98 results on '"Bonhomme-Faivre L"'
Search Results
2. Disposition of everolimus in mdr1a-/1b- mice and after a pre-treatment of lapatinib in Swiss mice
- Author
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Chu, C., Abbara, C., Noël-Hudson, M. S., Thomas-Bourgneuf, L., Gonin, P., Farinotti, R., and Bonhomme-Faivre, L.
- Published
- 2009
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3. Formulation of a Charcoal Suspension for Intratumor Injection. Part 1: Study of the Nature, Granulometry, and Concentration
- Author
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Bonhomme-Faivre, L., Mathieu, M. C., Grossiord, J. L., Depreatere, P., Couarraze, G., Orbach-Arbouys, S., Puisieux, F., and Seiller, M.
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- 1997
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4. Chronic administration of verapamil, ketoconazole and carbamazepine: impact on immunological parameters
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Bonhomme-Faivre, L., Forestier, F., Auchère, D., Soursac, M., Orbach-Arbouys, S., and Farinotti, R.
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- 2002
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5. Study of the correlation between MEIA and ELISA methods for FK 506 determination in liver transplant recipients
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Rudant, E., Bezie, Y., Bonhomme-Faivre, L., Manuel, N., Rucay, P., Fredj, G., and Bismuth, H.
- Published
- 1997
6. Pharmacokinetic Study of Raltegravir in HIV-Infected Patients With End-Stage Liver Disease: The LIVERAL-ANRS 148 Study
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Barau, Caroline, primary, Braun, Joséphine, additional, Vincent, Corine, additional, Haim-Boukobza, Stéphanie, additional, Molina, Jean-Michel, additional, Miailhes, Patrick, additional, Fournier, Isabelle, additional, Aboulker, Jean-Pierre, additional, Vittecoq, Daniel, additional, Duclos-Vallée, Jean-Charles, additional, Taburet, Anne-Marie, additional, Teicher, Elina, additional, Teicher, E., additional, Duclos-Vallée, J-C., additional, Aboulker, J-P., additional, Braun, J., additional, Fournier, I., additional, Vincent, C., additional, Arulananthan, A., additional, Eliette, V., additional, Euphrasie, F., additional, Guillon, B., additional, Ralaimazava, P., additional, Haïm-Boukobza, S., additional, Roque-Afonso, A-M., additional, Bonhomme-Faivre, L., additional, Rudant, E., additional, Taburet, A-M., additional, Aboulker, J.P., additional, Couffin-Cadiergues, S., additional, Delaugerre, C., additional, Durand, F., additional, Vittecoq, D., additional, Flandre, P., additional, Garraffo, R., additional, Ghosn, J., additional, Marraud, A., additional, Pageaux, G., additional, Derradji, O., additional, Bolliot, C., additional, Churaqui, F., additional, Antonini, T.M., additional, Coilly, A., additional, Ichai, P., additional, Ogier, O., additional, Belnard, M., additional, Molina, J-M., additional, De Lastours, V., additional, Gazaignes, S., additional, Ponscarme, D., additional, Sauvageon, H., additional, Miailhes, P., additional, Koffi, J., additional, Radenne, S., additional, and Brochier, C., additional
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- 2014
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7. P1237 ANTI-HEPATITIS C (HCV) TRIPLE THERAPY WITH PROTEASE INHIBITORS IN HIV/HCV CO-INFECTED PATIENTS AFTER LIVER TRANSPLANTATION
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Antonini, T.M., primary, Furlan, V., additional, Teicher, E., additional, Haim-Boukobza, S., additional, Sebagh, M., additional, Coilly, A., additional, Bonhomme-Faivre, L., additional, Roque-Afonso, A.-M., additional, Vittecoq, D., additional, Samuel, D., additional, Taburet, A.-M., additional, and Duclos-Vallee, J.-C., additional
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- 2014
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8. Étude du bon usage de l’agomélatine (Valdoxan®) à l’hôpital Paul-Brousse et à l’hôpital Paul-Guiraud (Villejuif)
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Bourguignon, E., primary, Rudant, E., additional, Gaudoneix-Taieb, M., additional, Beauverie, P., additional, and Bonhomme-Faivre, L., additional
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- 2012
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9. Generic drug prescriptions following hospital discharge: A prospective study in France
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Chu, C., primary, Rudant, E., additional, Bonvalet, M., additional, Agostini, H., additional, Cavalié, P., additional, Bonhomme-Faivre, L., additional, Frenkiel, J., additional, Taillandier, J., additional, Boissonnas, A., additional, Vittecoq, D., additional, and Wyplosz, B., additional
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- 2011
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10. N-03 Évaluation des prescriptions d’antibiotiques dans les services de médecine, maladies infectieuses et onco-hématologie dans un CHU en région parisienne
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Escaut, L., primary, Rudant, E., additional, Kassis-Chikhani, N., additional, Hache, C., additional, Bonhomme-Faivre, L., additional, Dussaix, E., additional, and Vittecoq, D., additional
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- 2009
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11. Disposition of everolimus in mdr1a−/1b− mice and after a pre-treatment of lapatinib in Swiss mice
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Chu, C., primary, Abbara, C., additional, Noël-Hudson, M.S., additional, Thomas-Bourgneuf, L., additional, Gonin, P., additional, Farinotti, R., additional, and Bonhomme-Faivre, L., additional
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- 2009
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12. Les médicaments génériques en sortie d’hospitalisation : enquête prospective chez 85malades à l’hôpital Paul-Brousse
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Chu, C., primary, Rudant, E., additional, Bonvalet, M., additional, Zavani, A., additional, Leplat, J., additional, Pfau, V., additional, Bonhomme-Faivre, L., additional, Taillandier, J., additional, Boissonnas, A., additional, Vittecoq, D., additional, and Wyplosz, B., additional
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- 2008
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13. Medico-pharmaceutical approach to reduce costs of infusion-related reactions (IRR) associated with cetuximab at Paul Brousse hospital
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Castagné, V., primary, Goldschmidt, E., additional, Lévi, F., additional, Brahimi, N., additional, Almohamad, W., additional, Machover, D., additional, Karaboué, A., additional, Habert, H., additional, Bonhomme-Faivre, L., additional, and Bouchahda, M., additional
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- 2008
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14. Valeur pronostique à 2 ans de l΄interleukine-6 dans une population de sujets âgés fragiles.
- Author
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Trivalle, C., Maurel, S., Taillandier, J., Rudant, E., and Bonhomme-Faivre, L.
- Abstract
Copyright of La Personne Agée Fragile is the property of Springer Nature / Books and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2009
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15. Symptômes rapportés par des utilisateurs de téléphones mobiles cellulaires
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Santini, R, primary, Seigne, M, additional, Bonhomme-Faivre, L, additional, Bouffet, S, additional, Defrasne, E, additional, and Sage, M, additional
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- 2001
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16. Charcoal suspension for tumor labelling modifies macrophage activity in mice
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Bonhomme-Faivre, L., primary, Depraetere, P., additional, Savelli, M.P, additional, Amdidouche, D., additional, Bizi, E., additional, Seiller, M., additional, and Orbach-Arbouys, S., additional
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- 2000
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17. Alterations of biological parameters in mice chronically exposed to low-frequency (50 HZ) electromagnetic fields
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Bonhomme-Faivre, L., primary, Macé, A., additional, Bezie, Y., additional, Marion, S., additional, Bindoula, G., additional, Szekely, A.M., additional, Frénois, N., additional, Auclair, H., additional, Orbach-Arbouys, S., additional, and Bizi, E., additional
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- 1998
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18. Formulation of a charcoal suspension for intratumoral injection: influence of the pluronic F68® concentration
- Author
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Bonhomme-Faivre, L, primary, Mathieu, M.C, additional, Depraetere, P, additional, Grossiord, J.L, additional, and Seiller, M, additional
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- 1997
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19. Pharmacokinetics of all-trans retinoic acid (ATRA) in patients with renal cancer concomitantly treated with interferon alpha 2A (IFN)
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Bonhomme-Faivre, L, primary
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- 1996
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20. Studies on toxicity of charcoal used in tattooing of tumors
- Author
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Bonhomme-Faivre, L., primary, Mathieu, M.C., additional, Arbouys, S.Orbach, additional, and Seiller, M., additional
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- 1996
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21. Effect of the ABCB1 3435C greater than T polymorphism on tacrolimus concentrations and dosage requirements in liver transplant recipients.
- Author
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Bonhomme-Faivre L, Picard V, Saliba F, Abbara C, Fodil M, Chaunoy M, and Farinotti R
- Abstract
Purpose. The effect of ABCB1 3435C>T on tacrolimus concentrations in liver transplant recipients was studied. Tacrolimus is a substrate for P-glycoprotein, the product of the ABCB1 gene. To determine whether the ABCB1 single-nucleotide polymorphism (SNP) 3435C>T was associated with variation in the tacrolimus concentration:dose ratio (C:D) in 42 liver transplant recipients during three months after transplantation. Methods. Forty-two Caucasian patients who underwent an orthotopic liver transplantation from cadaveric donors received a basic immunosuppressive regimen containing tacrolimus and corticosteroids; mycophenolate mofetil was added in 18 cases. The SNP 3435C>T in exon 26 was investigated by MboI restriction-enzyme digestion, leading to the identification of CC, TT, or CT status at nucleotide 3435. Results obtained for the three genotypes were compared for each of three values: daily weight-adjusted tacrolimus dose, blood trough tacrolimus concentration, and C:D. Results. The wild-type genotype (3435CC) was observed in 10 patients (24%); 23 patients (55%) were heterozygous (3435CT) and 9 patients (21%) were homozygous for the mutation (3435TT). One to three days after liver transplantation, the mean ± S.D. C:D was significantly higher in subjects homozygous for the mutation compared with subjects with the wild-type allele (236 ± 119 ng · kg/mL · mg versus 104 ± 74 ng · kg/mL · mg, respectively; p = 0.0167). Subjects with the heterozygous allele had an intermediate mean ± S.D. C:D (131 ± 108 ng · kg/mL · mg). One or three months after transplantation, no significant difference in the tacrolimus C:D was evident among the three groups. Conclusion. The ABCB1 3435C>T polymorphism influenced the tacrolimus C:D in the first days after liver transplantation. [ABSTRACT FROM AUTHOR]
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- 2009
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22. Hematologic and Cortisol Alterations Observed in Young Mice Placed in Front of a Color Television Screen#.
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Bonhomme-Faivre, L., Slama, C., Tanguy, M. L., Santini, R., Bezie, Y., Marion, S., Bottius, L., Pham, N. L., and Orbach-Arbouys, S.
- Subjects
- *
NEUTROPHILS , *HYDROCORTISONE , *ELECTROMAGNETIC fields , *LABORATORY mice , *TELEVISION , *MEDICINE - Abstract
Four-week-old Swiss male mice were placed 20 cm from a color television screen switched on for 5 continuous days/week, 9±5 h/Day for 106 days. The control group was nonexposed. The average magnetic field was 0.8 µT at the front of the exposed mice cage, and 0.23 µT at the back. Hematologic and cortisol values were measured on Days 0, 22, 57, and 106. Statistical analysis on weight and hematological values were performed using analysis of variance for repeated measures involving baseline values, group, time, and interaction between group and time as fixed factors. Polymorphonuclear neutrophils were significantly lower in the exposed group than control, but no interaction between time and exposure was found. On Day 22, erythrocytes, hemoglobin, hematocrit, and mean corpuscular hemoglobin were significantly higher in the exposed group. An exposed group were significantly higher than control, and on Day 106, values of the exposed group were significantly lower than control (Student t test). Such an observation could be explained by a feedback control following long-term irradiation exposure. In conclusion, exposure of very young mice to the electromagnetic emissions from a television screen appears to modify hamatological parameters, reaching values characteristic of adult mice. [ABSTRACT FROM AUTHOR]
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- 2004
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23. Interferon alfa-2a tretinoin in patients with metastatic renal cell carcinoma: a pilot study.
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Paule, B, Bonhomme-Faivre, L, Rudant, E, and Ferrière, F
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- 1997
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24. Nivolumab-induced pneumonitis and cardiopathy in a patient with relapsed Hodgkin's lymphoma.
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Bonhomme-Faivre L, Guarino V, and Misra SC
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- Humans, Female, Aged, Nivolumab adverse effects, Programmed Cell Death 1 Receptor, Stroke Volume, Ventricular Function, Left, Antibodies, Monoclonal adverse effects, Hodgkin Disease drug therapy, Pneumonia
- Abstract
Introduction: Nivolumab, the monoclonal antibody inhibitor of programmed cell death protein 1, enhances the T-cell response, including anti-tumour responses, by blocking the attachment of programmed death-ligand 1 and programmed death-ligand 2 ligands to the programmed cell death protein 1 receptor, which in turn leads to a reduction in tumour growth. Nivolumab has been approved in relapsed or refractory classic Hodgkin's lymphoma after autologous transplantation of haematopoietic stem cell and treatment with brentuximab as monotherapy., Case Report: We herewith report a case of 65-year-old woman who developed an interstitial pneumonitis and a global cardiac hypokinesis following a treatment with Nivolumab for a refractory Hodgkin's Lymphoma. Nivolumab was administered as the fifth line of therapy. Some concomitant patient treatments include drug with known autoimmune toxicities. Although the patient had a persistent complete remission following the sixth infusion, it was discontinued as she developed dyspnea of NYHA stage IV and orthopnea. The chest tomography revealed a bilateral micronodular pattern of organizing pneumonia with bilateral pleural effusion. The forced expiratory volume was decreased to 50%. In parallel her transthoracic echocardiography revealed a global hypokinesis with a left ventricular ejection fraction of 20%., Management and Outcome: The patient was treated with empiric antibiotics although the microbial assessments were negative. She was also treated with beta-blocker and angiotensin-converting enzyme inhibitors. The cardiac magnetic resonance imaging performed after 4 months confirmed the hypokinetic cardiopathy with an ejection fraction of 48%. The patient had a significant clinical improvement. The tomography emission positron scan conducted 8 months after interruption of Nivolumab showed complete remission with some moderate activation of residual lesion basal posterior lobe of left lung field., Discussion: Early and effective diagnosis of immune-related adverse events through the search for predictive biomarkers like drug factors and individual risk factors will allow targeted surveillance leading to a better tolerance.
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- 2023
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25. Acute Kidney Injury Following High-Dose Methotrexate Administration in a Day Care Hospital.
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Misra SC, Santagostino A, Dine G, and Bonhomme Faivre L
- Abstract
Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces medical costs substantially compared to inpatient care, which is driving the transfer of many inpatient chemotherapy protocols to day care hospitals (DCHs). However, in contrast to inpatient management, day care provides limited observation time, which could increase the risk of renal toxicity when using these protocols. We present a case report of acute kidney injury following high-dose methotrexate administration in a DCH. Based on a review of the current literature on acid-base balance, we also discuss appropriate patient selection and judicious hydration and urine alkalinization so as to prevent toxicity in the day care setting.
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- 2019
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26. Human-cell-derived organoids as a new ex vivo model for drug assays in oncology.
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Mebarki M, Bennaceur A, and Bonhomme-Faivre L
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- Animals, Biomimetics methods, Drug Evaluation, Preclinical methods, Humans, Antineoplastic Agents pharmacology, Drug Screening Assays, Antitumor methods, Medical Oncology methods, Neoplasms drug therapy, Organoids physiology
- Abstract
In oncology, a 2D in vitro model of cancer cell lines is still widely used for large-scale drug screening. However, most promising candidates firstly identified by in vitro analysis tend to fail during the next steps of drug development. The generation of an ex vivo approach termed 'organoid' is emerging as a promising preclinical model to mimic human tumors more accurately. In this review, we focus on human-derived organoid use for anticancer drug screening. We describe the development of this new in vitro model, its use for anticancer agent assays and the advantages compared with the currently used 2D models. Finally, we discuss organoid limitations in the common use of this technology during preclinical studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
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- 2018
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27. Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study.
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Tandia M, Mhiri A, Paule B, Saffroy R, Cailliez V, Noé G, Farinotti R, and Bonhomme-Faivre L
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- ATP Binding Cassette Transporter, Subfamily B genetics, Adult, Aged, Aged, 80 and over, Antineoplastic Agents pharmacokinetics, Breast Neoplasms drug therapy, DNA genetics, Drug Monitoring, Female, Genotype, Humans, Male, Middle Aged, Niacinamide pharmacokinetics, Niacinamide therapeutic use, Phenylurea Compounds pharmacokinetics, Polymorphism, Genetic genetics, Polymorphism, Single Nucleotide genetics, Protein Kinase Inhibitors pharmacokinetics, Sorafenib, Treatment Outcome, ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics, Antineoplastic Agents therapeutic use, Breast Neoplasms genetics, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Neoplasm Proteins genetics, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use, Protein Kinase Inhibitors therapeutic use
- Abstract
Objectives: We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma., Methods: At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography. All enrolled patients were genotyped for ABCB1 (rs2032582; rs1045642) and ABCG2 (rs2231137; rs2231142; rs2622604) by blood genomic DNA extraction and Mass ARRAY genotyping. The clinical response was evaluated after 3months of treatment according to the RECIST criteria., Key Findings: Significant associations between sorafenib exposure and the studied polymorphisms were observed for ABCB1 3435C>T, ABCG2 34G>A, ABCG2 1143C>T and ABCG2 421C>A, but not for ABCB1 2677G>TA SNP. In heterozygous patients for ABCB1 3435 C>T, ABCG2 34 G>A and ABCG2 1143 C>T polymorphisms were significantly associated with the lowest sorafenib plasma levels. Those patients presented a tendency to have the best clinical evolution., Conclusion: Heterozygous forms of the studied polymorphisms could be associated with a better therapeutic response.
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- 2017
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28. Therapy with boceprevir or telaprevir in HIV/hepatitis C virus co-infected patients to treat recurrence of hepatitis C virus infection after liver transplantation.
- Author
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Antonini TM, Furlan V, Teicher E, Haim-Boukobza S, Sebagh M, Coilly A, Bonhomme-Faivre L, Roque-Afonso AM, Vittecoq D, Samuel D, Taburet AM, and Duclos-Vallée JC
- Subjects
- Adult, Coinfection drug therapy, Cyclosporine therapeutic use, Drug Therapy, Combination, Female, Humans, Immunosuppression Therapy, Interferon alpha-2, Interferon-alpha therapeutic use, Male, Middle Aged, Polyethylene Glycols therapeutic use, Proline therapeutic use, Recombinant Proteins therapeutic use, Recurrence, Ribavirin therapeutic use, Tacrolimus therapeutic use, Viral Load, Antiviral Agents therapeutic use, HIV Infections drug therapy, Hepatitis C, Chronic drug therapy, Liver Transplantation adverse effects, Oligopeptides therapeutic use, Proline analogs & derivatives
- Abstract
Objective: Severe hepatitis C virus (HCV) recurrence affects post-transplant survival in HIV/HCV co-infected patients. This article describes the results of triple anti-HCV therapy with boceprevir or telaprevir in seven HIV/HCV co-infected patients following liver transplantation., Methods: All patients had severe HCV recurrence [fibrosis stage ≥F2 or acute hepatitis ≥A2 (n = 5) or fibrosing cholestatic hepatitis (n = 2)] associated with genotype 1a (n = 4) or 1b (n = 3). Patients were treated with Peg-interferon/ribavirin and boceprevir (n = 2) or telaprevir (n = 5) immediately (n = 3) or after a 4-week lead-in phase (n = 4). Immunosuppression included either cyclosporine (n = 5) or tacrolimus (n = 2). Prior to introducing telaprevir, combined antiretroviral therapy was switched in one patient to prevent drug-drug interactions., Results: At 24 weeks after the end of treatment, sustained virological response was observed in 60% (3/5) of the patients treated with telaprevir; no responders were observed in the boceprevir group. Triple anti-HCV therapy was prematurely discontinued in six patients [treatment failure (n = 2), infection (n = 2), acute rejection (n = 1) and myocardial infarction (n = 1)]. Anaemia occurred in all patients, requiring erythropoietin, ribavirin dose reduction and red blood cell transfusions in five patients.Average cyclosporine doses were reduced by 50-84% after telaprevir initiation and by 33% after boceprevir initiation. Tacrolimus doses were reduced by 95% with telaprevir., Conclusion: Our data suggest that in HIV/HCV co-infected patients, triple anti-HCV therapy with telaprevir greatly improved efficacy despite poor tolerability. Significant decreases in cyclosporine or tacrolimus doses are necessary prior to introduction of boceprevir or telaprevir. Close monitoring is essential to prevent drug-drug interactions among antiretroviral therapy, immunosuppressive agents and anti-HCV therapy.
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- 2015
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29. Cetuximab increases concentrations of irinotecan and of its active metabolite SN-38 in plasma and tumour of human colorectal carcinoma-bearing mice.
- Author
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Chu C, Abbara C, Tandia M, Polrot M, Gonin P, Farinotti R, and Bonhomme-Faivre L
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- ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors, Administration, Oral, Animals, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols pharmacology, Area Under Curve, Biological Transport drug effects, Camptothecin pharmacokinetics, Camptothecin pharmacology, Cetuximab, Colorectal Neoplasms pathology, Drug Interactions, Drug Resistance, Neoplasm drug effects, Female, Humans, Irinotecan, Mice, Mice, Nude, Tissue Distribution, Xenograft Model Antitumor Assays, Antibodies, Monoclonal, Humanized pharmacology, Camptothecin analogs & derivatives, Colorectal Neoplasms drug therapy
- Abstract
In a previous study, we showed that cetuximab, a monoclonal antibody directed towards epidermal growth factor receptor, could inhibit P-glycoprotein (P-gp), an efflux protein of ATP-binding cassette family, and lead to an increased P-gp substrate intracellular concentration. Cetuximab is given with irinotecan to patients with metastasis colorectal cancer who did not respond to irinotecan-based therapy. The mechanism of this successful clinical reversion remains unknown. As irinotecan is a P-gp substrate, we tested here whether cetuximab could modify irinotecan concentration in mice. Therefore, concentrations of irinotecan and of its active metabolite SN-38 were measured by HPLC in plasma and tumour of mice bearing a human colorectal carcinoma xenograft when irinotecan is given orally alone or after a pretreatment with cetuximab. Pharmacokinetic analysis showed no significant modification of irinotecan concentrations but a significant increase (1.7-fold) in SN-38 AUCs in plasma and in tumour after a pretreatment with cetuximab. Those results suggest that cetuximab influence irinotecan distribution into tissues probably due to inhibition of P-gp. As SN-38 is 200-fold more potent than irinotecan, cetuximab could reverse irinotecan resistance by an effect on its active metabolite. Inhibiting SN-38 efflux by P-gp drug transporters in biliary system and tumour can lead to pharmacokinetic modification and a higher anticancer efficacy., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)
- Published
- 2014
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30. Successful anti-hepatitis C virus therapy with telaprevir in an HIV/hepatitis C virus co-infected patient with a severe recurrence of hepatitis C virus infection on the liver graft.
- Author
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Antonini TM, Furlan V, Teicher E, Haim-Boukobza S, Sebagh M, Coilly A, Bonhomme-Faivre L, Peytavin G, Roque-Afonso AM, Vittecoq D, Samuel D, Taburet AM, and Duclos-Vallée JC
- Subjects
- Drug Therapy, Combination methods, Female, Humans, Interferon-alpha therapeutic use, Liver Transplantation, Middle Aged, Polyethylene Glycols therapeutic use, RNA, Viral blood, Recombinant Proteins therapeutic use, Ribavirin therapeutic use, Transplantation, Treatment Outcome, Viral Load, Antiviral Agents therapeutic use, HIV Infections complications, Hepatitis C drug therapy, Oligopeptides therapeutic use
- Abstract
We report, for the first time, the outcome of anti-hepatitis C virus (HCV) triple therapy with telaprevir in an HIV/HCV co-infected transplanted patient. After liver transplantation, the patient experienced a severe HCV recurrence with fibrosing cholestatic hepatitis, and anti-HCV therapy with pegylated interferon alpha 2a, ribavirin and telaprevir was initiated. A sustained virological response was achieved after 48 weeks of anti-HCV therapy. Drug-drug interactions between antiretroviral therapy, immunosuppressive agents and anti-HCV therapy could be managed.
- Published
- 2013
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31. Therapeutic efficiency of everolimus and lapatinib in xenograft model of human colorectal carcinoma with KRAS mutation.
- Author
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Chu C, Noël-Hudson MS, Boige V, Goéré D, Marion S, Polrot M, Bigot L, Gonin P, Farinotti R, and Bonhomme-Faivre L
- Subjects
- ATP Binding Cassette Transporter, Subfamily B metabolism, Animals, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Drug Resistance, Neoplasm, Everolimus, Female, Humans, Lapatinib, Mice, Mice, Nude, Mutation, Quinazolines administration & dosage, Sirolimus administration & dosage, Sirolimus pharmacology, Xenograft Model Antitumor Assays, ras Proteins metabolism, Antineoplastic Combined Chemotherapy Protocols pharmacology, Colorectal Neoplasms drug therapy, Quinazolines pharmacology, Sirolimus analogs & derivatives, ras Proteins genetics
- Abstract
KRAS mutation is a negative predictive prognostic factor during metastatic colorectal cancer treatment with antiepidermal growth factor receptor antibodies. For affected patients, new therapeutics must be explored. Our objective was to study efficacy of two drugs with different mechanisms of action, everolimus (mTOR inhibitor) and lapatinib (tyrosine kinase inhibitor), in a mouse xenograft model. We chose a model obtained after engraftment of a tumor originating from a human tumor collection. The patient was affected by a metastasis colorectal carcinoma resistant to cetuximab with KRAS mutation. From a previous study in mice, we know that everolimus is a P-glycoprotein (P-gp) substrate and that a lapatinib pretreatment increases significantly (2.6-fold) everolimus AUC by inhibiting its intestinal P-gp efflux. We hence tested the effect of these drugs alone or combined. Mice bearing the xenografts were divided in four groups: control, lapatinib, everolimus, and L/E group (L/E: 2 days of lapatinib 200 mg/kg and then 3 days of everolimus 1 mg/kg). Tumor volumes and treatment toxicities were evaluated. Sixteen days after treatment initiation, the group L/E was the first one in which tumor volume average was significantly lower than the one of control group (193 ± 90 vs. 395 ± 171 mm(3) ; P = 0.0025). After 4 weeks of treatment, inhibition of tumor growth in lapatinib, everolimus, and L/E groups reached, respectively, 49, 53, and 57%. Each drug showed significant antitumor activity. Only moderate hematologic toxicity signs were observed. These results lead to new perspectives for new oral drugs in metastatic KRAS-mutated colorectal cancer resistant to standard chemotherapy., (© 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
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32. Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence.
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Coilly A, Furlan V, Roche B, Barau C, Noël C, Bonhomme-Faivre L, Antonini TM, Roque-Afonso AM, Samuel D, Taburet AM, and Duclos-Vallée JC
- Subjects
- Aged, Antiviral Agents pharmacology, Cyclosporine pharmacology, Cyclosporine therapeutic use, Disease Management, Drug Therapy, Combination, Everolimus, Hepacivirus growth & development, Hepatitis C, Chronic immunology, Hepatitis C, Chronic virology, Humans, Immunosuppressive Agents pharmacology, Interferon-alpha pharmacology, Interferon-alpha therapeutic use, Male, Middle Aged, Polyethylene Glycols pharmacology, Polyethylene Glycols therapeutic use, Proline analogs & derivatives, Proline pharmacology, Proline therapeutic use, Recombinant Proteins pharmacology, Recombinant Proteins therapeutic use, Recurrence, Ribavirin pharmacology, Ribavirin therapeutic use, Sirolimus analogs & derivatives, Sirolimus pharmacology, Sirolimus therapeutic use, Tacrolimus pharmacology, Tacrolimus therapeutic use, Viral Load drug effects, Antiviral Agents therapeutic use, Hepacivirus drug effects, Hepatitis C, Chronic drug therapy, Immunosuppressive Agents therapeutic use, Liver Transplantation immunology
- Abstract
Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ± 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ± 2.27 g/dl. All patients required administration of β-erythropoietin (n = 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ± 0.35 log(10) IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT.
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- 2012
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33. Interferon-alpha improves docetaxel antitumoral and antimetastatic efficiency in Lewis lung carcinoma bearing mice.
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Ben Reguiga M, Bouquet C, Farinotti R, and Bonhomme-Faivre L
- Subjects
- Animals, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents pharmacology, Carcinoma, Lewis Lung pathology, Cell Line, Tumor, Docetaxel, Immunologic Factors pharmacology, Interferon-alpha pharmacology, Kaplan-Meier Estimate, Lung drug effects, Lung pathology, Lung Neoplasms pathology, Mice, Mice, Inbred C57BL, Neoplasm Metastasis drug therapy, Taxoids pharmacokinetics, Taxoids pharmacology, Antineoplastic Agents therapeutic use, Carcinoma, Lewis Lung drug therapy, Immunologic Factors therapeutic use, Interferon-alpha therapeutic use, Lung Neoplasms drug therapy, Taxoids therapeutic use
- Abstract
Aims: Interferon-alpha (IFN-α) was shown to reduce P-glycoprotein (P-gp) expression and activity in several tissues. The purpose of this study was to evaluate the impact of IFN-α pretreatment on the antitumoral and antimetastatic, Docetaxel (DTX, P-gp substrate), on Lewis Lung Cancer (3LL) bearing mice and to correlate it to DTX pharmacokinetics., Main Methods: Six groups of C57/Bl6 mice received subcutaneous (s.c.) 2.10(6) 3LL cells, then IFN-α 4MIU/kg for 7days, then received or did not receive i.v. or oral DTX (30mg/kg). Pharmacokinetic studies were done on a part of the mice: DTX concentrations were assessed in plasma and tumors, where AUC were estimated with the Bailer method, and half-lives and MRT were determined with a non-compartmental analysis. Tumor growth was assessed more than 21days: animals were then sacrificed and lung metastases number was counted. Kaplan-Meier analysis was made to analyze survival data during the survey period., Key Findings: DTX i.v. associated with IFN-α significantly improved mouse survival (19.6±0.6days vs. 17.1±0.8days for control mice, p=0.047) with greater antimetastatic effects (87.5% reduction in the number of metastases compared to control mice). The effect on tumor growth was not modified within the IFN-α/DTX i.v. treated groups when compared to mice receiving DTX i.v. alone. The pharmacokinetic analysis showed an increase of DTX concentrations in tumors at 30min after DTX i.v. administration and an increase in the oral bioavailability of orally given DTX following an IFN-α treatment., Significance: Our study established that IFN-α increases DTX uptake in tumors, improves its antitumoral efficiency and improves animals' survival., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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34. Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step.
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Castagne V, Habert H, Abbara C, Rudant E, and Bonhomme-Faivre L
- Subjects
- Antineoplastic Agents administration & dosage, Asepsis standards, Cytotoxins administration & dosage, Drug Compounding standards, France, Humans, Infusions, Intravenous, Quality Assurance, Health Care standards, Quality Control, Reproducibility of Results, Retrospective Studies, Time Factors, Antineoplastic Agents standards, Chromatography, High Pressure Liquid standards, Cytotoxins standards, Drug Contamination prevention & control, Hospitals, University standards, Pharmacy Service, Hospital standards
- Abstract
The Centralized Chemotherapy Reconstitution Unit (CCRU) of Paul Brousse Hospital Pharmacy Department assessed the reliability of its Cytotoxics Compounded Sterile Products (CCSP) preparation method in order to improve its CCSP quality assurance system. Five cytotoxic drugs - gemcitabine, 5-fluorouracil, docetaxel, paclitaxel, and oxaliplatin - were assayed by high performance liquid chromatography (HPLC) to determine CCSP concentration. During the observation period, 23,892 CCSP were prepared. Overall, 12,964 preparations contained one of the five analyzed drugs; 7382 (56.9%) out of 12,964 CCSP were analyzed by HPLC; 646 (8.8%) out of 7382 concentrations were outside ± 20% of the prescribed dose; 544 (84.2%) out of 646 were post-administration results and could not be verified. Out of 102 (15.8%) pre-administration results that were re-tested after re-shaking, 94 (92.2%) were found to be acceptable upon re-testing, and 8 (7.8%) were confirmed to be unacceptable and needed to be re-compounded. The 8.8% of tested CCSP were outside ± 20% of the prescribed dose, but extrapolating the results on re-tested CCSP, we can say that our CCSP preparation is reliable with an estimation of only 0.7% of 7382 CCSP analyzed, confirmed as being ± 20% outside the prescribed dose. Nevertheless, this ± 20% magnitude of error should be reduced. Based on pre-administration results, the primary cause of concentration errors appeared to be insufficient mixing of the finished product. Most CCSP dosages occurred after it had been administered, the organization should, therefore, be improved to include testing all CCSP prior to administration. Pharmaceutical companies should endeavor to manufacture compounded injectible drugs in a 'ready to use' form and provide vehicles in accurate volumes in order to improve compounding precision.
- Published
- 2011
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35. Significance of isolated hepatic veno-occlusive disease/sinusoidal obstruction syndrome after liver transplantation.
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Sebagh M, Azoulay D, Roche B, Hoti E, Karam V, Teicher E, Bonhomme-Faivre L, Saliba F, Duclos-Vallée JC, and Samuel D
- Subjects
- Adolescent, Adult, Biopsy, Female, Graft Rejection, Hepatic Veno-Occlusive Disease complications, Humans, Immunosuppressive Agents therapeutic use, Liver Failure complications, Male, Middle Aged, Prevalence, Prognosis, Retrospective Studies, Hepatic Veno-Occlusive Disease surgery, Liver Failure surgery, Liver Transplantation methods
- Abstract
After liver transplantation (LT), hepatic veno-occlusive disease (VOD), which is also known as sinusoidal obstruction syndrome (SOS), has been reported initially in relation to azathioprine use and subsequently in relation to acute rejection (AR). Isolated veno-occlusive disease (iVOD)/SOS raises some questions about its significance and especially its treatment. From the post-LT biopsy samples of 1364 patients (2000-2008), 31 patients with index biopsy samples showing VOD/SOS (2.3%) were identified. After a review of the index biopsy samples and previous biopsy samples, those patients not exposed to azathioprine therapy were subdivided into 2 groups according to the absence or presence of AR. Fifteen of the 31 patients had no previous evidence of AR, whereas 16 experienced episodes of AR (before or concurrently with VOD). The 2 groups were similar in terms of demographic and clinical data and the range of histological centrilobular changes. AR episodes were characterized by an endothelial predilection. iVOD/SOS occurred later than acute rejection-related veno-occlusive disease (AR-VOD)/SOS (mean times of 65 and 4.4 months, respectively, P = 0.0098). There was a tendency for iVOD/SOS to progress less frequently to chronic rejection in comparison with AR-VOD/SOS (3/15 versus 9/15, P = 0.06). The histological resolution of iVOD/SOS was significantly more frequent in patients who benefited from increased immunosuppression in comparison with those who did not (5/7 versus 2/8, P = 0.05). When the groups were considered together, the same result was obtained (14/18 versus 4/12, P = 0.024). In conclusion, despite a constant overall prevalence of VOD/SOS, the proportion of iVOD/SOS has increased. The histological resolution of iVOD/SOS after increase in immunosuppression suggests an immune-mediated origin. Better optimization of immunosuppression may be a curative treatment., (Copyright © 2011 American Association for the Study of Liver Diseases.)
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- 2011
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36. Ultra-resistant schizophrenia is not associated with the multidrug-resistant transporter 1 (MDR1) gene rs1045642 variant.
- Author
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Mouaffak F, Kebir O, Picard V, Bonhomme-Faivre L, Millet B, Olié JP, Reynaud M, Krebs MO, and Benyamina A
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Adult, Antipsychotic Agents therapeutic use, Drug Resistance genetics, Female, Humans, Male, Schizophrenia drug therapy, Young Adult, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Genetic Variation genetics, Polymorphism, Genetic genetics, Schizophrenia genetics
- Published
- 2011
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37. MDR1 polymorphism role in patients treated with cetuximab and irinotecan in irinotecan refractory colorectal cancer.
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Paule B, Castagne V, Picard V, Saffroy R, Adam R, Guettier C, Farinotti R, and Bonhomme-Faivre L
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Humanized, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Cetuximab, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, ErbB Receptors metabolism, Female, Humans, Immunoenzyme Techniques, Irinotecan, Liver Neoplasms drug therapy, Liver Neoplasms secondary, Male, Middle Aged, Neoplasm Staging, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), Survival Rate, Treatment Outcome, ras Proteins genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colorectal Neoplasms genetics, Drug Resistance, Neoplasm genetics, Liver Neoplasms genetics, Polymorphism, Genetic drug effects
- Abstract
The aim of the study was to evaluate the influence of the MDR1 C3435T polymorphism on the therapeutic response in 23 patients treated with cetuximab plus irinotecan for irinotecan refractory liver metastatic colorectal cancer considering their KRAS status. Indeed, irinotecan and its active metabolite (SN-38) are both substrates of P-glycoprotein (P-gp) encoded by MDR1. Patients received cetuximab and irinotecan up to progression. The overall survival was 55% at 10 months. Overall, four patients had an undetermined KRAS status and two patients with mutated KRAS were in progression disease. The response to treatment was observed after 3 months among the 17 wild-type KRAS patients. Two patients presented a progressive disease (1 TT and 1 CT), eight patients had a stable disease (5 CC and 3CT) and five patients had a partial response (3 CC and 2 CT). Importantly, 2 patients (2 TT) were in complete response and still alive 5 years after starting the treatment, which suggests that the combination of wild-type KRAS and MDR1 3435 TT may be a factor of good prognosis. These results suggest that EGFR inhibition by cetuximab may overcome this irinotecan resistance by abrogating drug efflux depending on MDR1 3435 polymorphism. Among patients resistant to irinotecan, it is still possible to use the association of cetuximab plus irinotecan to obtain a complete resection of hepatic metastases that is necessary to improve their survival.
- Published
- 2010
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38. Interleukin-2 treatment effect on imatinib pharmacokinetic, P-gp and BCRP expression in mice.
- Author
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Hosten B, Abbara C, Cibert M, Petit B, Farinotti R, Gonin P, and Bonhomme-Faivre L
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1, ATP Binding Cassette Transporter, Subfamily G, Member 2, Administration, Oral, Animals, Antineoplastic Agents administration & dosage, Benzamides, Blotting, Western, Female, Imatinib Mesylate, Mice, Mice, Inbred C57BL, Piperazines administration & dosage, Pyrimidines administration & dosage, Recombinant Proteins pharmacology, Tissue Distribution, ATP-Binding Cassette Transporters metabolism, Antineoplastic Agents pharmacokinetics, Interleukin-2 pharmacology, Piperazines pharmacokinetics, Pyrimidines pharmacokinetics
- Abstract
The aim of this study was to investigate the effect that recombinant interleukin-2 (rIL-2) (0.16 MUI/injection) had on the pharmacokinetics of imatinib (IM) in plasma. In this study, IM was given orally to mice at a dose of 150 mg/kg once a day for 11 days (from day 1 to 11) either alone or in combination with intraperitoneal injections of rIL-2 twice a day from day 8 to 11. Pharmacokinetic parameters were determined using WinNonLin software. Areas under the curve were compared using Bailer's method. The repeated administration of the rIL-2+IM combination was shown to have two pharmacokinetic advantages compared with repeated IM doses alone. In addition to the pharmacodynamic interest of this treatment, we found that the combined treatment significantly increased the IM Cmax (P<0.05) and significantly increased the IM trough concentration (C(24 h)) (P<0.01), which was always above the minimum therapeutic IM concentration (1 mumol/l) in plasma. Those pharmacokinetic modifications may be explained, in part, by a decrease in the P-glycoprotein expression in the three intestinal segments of the mice (duodenum, P<0.01; jejunum, P<0.05; and ileum, P<0.05) and a decrease in BCRP expression in the duodenum segment (P<0.05) due to rIL-2. In another experiment, we found a significant induction of intestinal P-glycoprotein expression in mice that had been given IM orally (150 mg/kg) twice a day for 11 days. It would be interesting to further investigate the IM disposition associated with rIL-2 treatment for clinical applications.
- Published
- 2010
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39. Enfuvirtide: a safe and effective antiretroviral agent for human immunodeficiency virus-infected patients shortly after liver transplantation.
- Author
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Teicher E, Abbara C, Duclos-Vallée JC, Antonini T, Bonhomme-Faivre L, Desbois D, Samuel D, and Vittecoq D
- Subjects
- Adult, Cyclosporine therapeutic use, Dose-Response Relationship, Drug, Enfuvirtide, Female, Humans, Immunosuppressive Agents therapeutic use, Lopinavir, Male, Middle Aged, Pyrimidinones therapeutic use, Ritonavir therapeutic use, Tacrolimus therapeutic use, Treatment Outcome, Anti-Retroviral Agents therapeutic use, HIV Envelope Protein gp41 therapeutic use, HIV Infections complications, HIV Infections drug therapy, Liver Failure complications, Liver Failure therapy, Liver Transplantation methods, Peptide Fragments therapeutic use
- Abstract
The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV)-coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir-exposed patients. During period 1, tacrolimus and cyclosporine A doses were 8 and 600 mg/day, respectively, and the trough concentrations were within the therapeutic range in both groups. In period 2, the addition of lopinavir/ritonavir to the immunosuppressant regimen enabled a reduction in the dose of immunosuppressants required to maintain trough concentrations within the therapeutic range (to 0.3 mg/day for tacrolimus and 75 mg/day for cyclosporine). Immunosuppressant doses were not modified by the reintroduction of enfuvirtide, there being no change in the mean trough concentrations over the 3 periods. CD4 cell counts remained at about 200 cells/mm3. The HIV RNA viral load remained undetectable. Both groups displayed signs of mild cytolysis and cholestasis due to the recurrence of HCV, whereas no renal insufficiency was observed. Enfuvirtide is an attractive alternative to standard ARV therapy, facilitating the management of drug-drug interactions shortly after liver transplantation. Moreover, the lack of liver toxicity renders this drug valuable in the event of a severe HCV recurrence., (Copyright 2009 AASLD)
- Published
- 2009
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40. Association between ABCB1 C3435T polymorphism and increased risk of cannabis dependence.
- Author
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Benyamina A, Bonhomme-Faivre L, Picard V, Sabbagh A, Richard D, Blecha L, Rahioui H, Karila L, Lukasiewicz M, Farinotti R, Picard V, Marill C, and Reynaud M
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Adolescent, Adult, Aged, Analysis of Variance, DNA Mutational Analysis, Dronabinol blood, Female, Follow-Up Studies, Gas Chromatography-Mass Spectrometry methods, Gene Frequency, Genotype, Humans, Male, Marijuana Abuse blood, Middle Aged, Odds Ratio, Risk Factors, Statistics, Nonparametric, Young Adult, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Genetic Predisposition to Disease, Marijuana Abuse genetics, Polymorphism, Single Nucleotide genetics
- Abstract
Prolonged cannabis use has a significant impact on health and well-being. Genetic factors are known to influence cannabis dependence, but few specific genetic markers have been identified. ABCB1 polymorphisms are known to modify drug pharmacokinetics but have yet to be studied for their role in generating and maintaining cannabis dependence. The objective of this study is to determine if ABCB1 C3435T polymorphism may represent an independent genetic marker for cannabis dependence risk. An open bi-centric association study was conducted in two French Addiction Centres. Caucasian patients diagnosed with isolated cannabis dependence were compared with healthy age-matched controls for socio-demographic, clinical and genetic data using chi-square test, Fisher's exact test, or Mann-Whitney U test. Independent association between ABCB1 C3435T SNP marker and cannabis dependence was evaluated using multiple logistic regression analysis. Versus controls (n=40), patients with cannabis dependence (n=40) had a significantly higher 3435C allele frequency (62.5% versus 43.8% respectively, P=0.017) and CC genotype (50% versus 20%, P=0.005, OR=4.00 [1.50-10.60]). Multiple logistic regression analysis of the C3435T SNP and variables identified in univariate analyses indicated that the CC genotype was independently associated with cannabis dependence (P=0.045, OR=6.61 [1.05-46.58]). This is the first time a significant specific genetic marker has been shown in cannabis dependence. ABCB1 polymorphisms may alter Delta9THC distribution, its psychoactive effects and individual vulnerability to dependence. These results pave the way to a new pharmacogenetic hypothesis in cannabis dependence.
- Published
- 2009
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41. Disposition of Delta tetrahydrocannabinol in CF1 mice deficient in mdr1a P-glycoprotein.
- Author
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Bonhomme-Faivre L, Benyamina A, Reynaud M, Farinotti R, and Abbara C
- Subjects
- Animals, Digoxin administration & dosage, Digoxin pharmacokinetics, Dronabinol blood, Endothelium, Vascular metabolism, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors pharmacokinetics, Hallucinogens blood, Injections, Intestinal Mucosa metabolism, Mice, Time Factors, ATP Binding Cassette Transporter, Subfamily B deficiency, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Chloroplast Proton-Translocating ATPases metabolism, Dronabinol pharmacokinetics, Hallucinogens pharmacokinetics, Proteoglycans metabolism
- Abstract
P-glycoprotein (P-gp) plays a major role in drug efflux. All the transported substrates are more or less hydrophobic and amphiphatic in nature. Being lipophilic, Delta(9) tetrahydrocannabinol (THC), the main cannabis component, could be a potential P-gp substrate. The aim of this project was to determine the contribution of the mdr1a gene product to THC disposition. Therefore, oral THC and digoxin (substrate test for P-gp) pharmacokinetics have been investigated in the intestinal epithelium and in the brain capillary endothelium of CF1 mdr1a-/- mice (mice naturally deficient in P-gp). These pharmacokinetics were compared to THC and digoxin oral pharmacokinetics in wild type mice mdr1a+/+ (not P-gp deficient). The application of Bailer's method showed that THC total exposure measured by the area under the plasma concentration time curve was 2.17-fold higher in CF1 mice naturally deficient in P-gp than in wild type mice after oral administration of 25 mg/kg of THC, and 2.4-fold higher after oral administration of 33 microg/kg of digoxin. As a consequence, the oral bioavailability of THC and digoxin was higher in naturally P-gp-deficient mice. We concluded that P-gp limits THC oral uptake and mediates direct drug excretion from the systemic circulation into the intestinal lumen.
- Published
- 2008
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42. Effect of interleukin-2 pretreatment on paclitaxel absorption and tissue disposition after oral and intravenous administration in mice.
- Author
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Hosten B, Abbara C, Petit B, Dauvin A, Bourasset F, Farinotti R, Gonin P, and Bonhomme-Faivre L
- Subjects
- Administration, Oral, Animals, Antineoplastic Agents, Phytogenic administration & dosage, Blotting, Western, Female, Infusions, Intravenous, Mice, Mice, Inbred C57BL, Paclitaxel administration & dosage, Recombinant Proteins pharmacology, Tissue Distribution, Antineoplastic Agents, Phytogenic pharmacokinetics, Interleukin-2 pharmacology, Paclitaxel pharmacokinetics
- Abstract
The aim of the present study was to investigate the effects of recombinant interleukin (rIL)-2 treatment on paclitaxel (PLX) pharmacokinetics in the plasma and tissue of Lewis lung carcinoma-bearing mice (lung tissues and s.c. tumors). PLX pharmacokinetics studies were conducted after oral and i.v. administration of 15 and 4 mg/kg, respectively, either alone or after 3 days of rIL-2 pretreatment. The noncompartmental approach was used to determine the mean pharmacokinetic parameters using WinNonlin software (Pharsight, Mountain View, CA). The influence of rIL-2 pretreatment on physiological P-glycoprotein (P-gp) expression in lung and intestine was investigated by Western blot analysis. After oral administration of PLX, areas under the curve (AUC) in plasma, lung, and s.c. tumors were significantly higher (2.98, 2.66, and 3.41-fold, respectively) in the rIL-2 + PLX group as compared with the PLX group. However, no significant effect of rIL-2 pretreatment was observed in plasma or lung following i.v. administration of PLX. PLX AUC in s.c. tumors was significantly higher (1.37-fold) with rIL-2 pretreatment as compared with the PLX-alone group after i.v. injection. Pretreatment with rIL-2 appeared to have no effect on PLX plasma terminal half-life when PLX was administered orally or i.v. However, prolongation of PLX terminal half-life estimated from lung and s.c. tumors data had been observed. Increased PLX tissue absorption in the rIL-2-pretreated group may be explained by a decrease of P-gp expression in the intestines and lung or decreased functionality due to rIL-2. Oral administration allowed the targeted tissues a much higher PLX exposure as compared with i.v. administration.
- Published
- 2008
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43. Tattooing breast cancers treated with neoadjuvant chemotherapy.
- Author
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Mathieu MC, Bonhomme-Faivre L, Rouzier R, Seiller M, Barreau-Pouhaer L, and Travagli JP
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Axilla surgery, Biopsy, Needle, Breast Neoplasms diagnosis, Breast Neoplasms surgery, Charcoal adverse effects, Chemotherapy, Adjuvant, Cyclophosphamide administration & dosage, Diffusion, Doxorubicin administration & dosage, Female, Fluorouracil administration & dosage, Humans, Hydrogen-Ion Concentration, Injections, Intralesional, Mastectomy, Segmental, Methotrexate administration & dosage, Particle Size, Suspensions, Treatment Outcome, Vincristine administration & dosage, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Charcoal chemistry
- Abstract
Background: In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy., Methods: In a series of 109 patients with large breast tumors, a 4% or 10% charcoal suspension was injected at the time of the initial biopsy before preoperative chemotherapy., Results: Tolerance was good. After three or four cycles of chemotherapy, 91 patients underwent conservative treatment, and the surgical specimen was examined intraoperatively. The charcoal was detected in 94% of the cases. The charcoal was seen in the nodule or at the periphery in the surgical specimen without any acute inflammatory reaction or diffusion., Conclusions: On the basis of these results, this micronized charcoal suspension at a defined granulometry and a concentration of 10% seems to be ideal for tattooing breast carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy is planned.
- Published
- 2007
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44. Prognostic value of serum interleukin-6 (IL-6) levels in long term care.
- Author
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Maurel S, Hamon B, Taillandier J, Rudant E, Bonhomme-Faivre L, and Trivalle C
- Subjects
- Aged, Aged, 80 and over, Biomarkers blood, Cross-Sectional Studies, Female, Frail Elderly, France epidemiology, Humans, Male, Prognosis, Retrospective Studies, Sex Factors, Survival Rate trends, Interleukin-6 blood, Long-Term Care
- Abstract
The aim of this prospective study was to examine the relationship between IL-6 levels and survival in an elderly population in a long term hospital care ward. All of the 184 women and 65 men hospitalized in the geriatric unit regardless of their health status were included. The plasma levels of interleukin-6 were measured at baseline and deaths were assessed over a 2-year period. IL-6 levels of at least 3pg/ml in men and 5.6pg/ml in women were respectively associated with a relative risk of death of 2.28 (CI(95): 1.04-4.95) and 1.52 (CI(95): 1.06-2.18). After adjustment for age class, the reduced survival observed with these thresholds only remained unchanged in men, the difference in survival in women was not significant. Our conclusion is that even in an elderly hospitalized population, high IL-6 levels were associated with poor survival. The lower survival rate after adjustment for class of age found in men but not in women suggests a gender-related specificity.
- Published
- 2007
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45. Bioavailability and tissular distribution of docetaxel, a P-glycoprotein substrate, are modified by interferon-alpha in rats.
- Author
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Ben Reguiga M, Bonhomme-Faivre L, and Farinotti R
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 drug effects, Administration, Oral, Animals, Antineoplastic Agents administration & dosage, Biological Availability, Docetaxel, Drug Interactions, Female, Infusions, Intravenous, Interferon alpha-2, Polyethylene Glycols, Rats, Rats, Sprague-Dawley, Recombinant Proteins, Taxoids administration & dosage, Tissue Distribution, Antineoplastic Agents pharmacokinetics, Antiviral Agents administration & dosage, Interferon-alpha administration & dosage, Taxoids pharmacokinetics
- Abstract
Interferon-alpha (IFN-alpha) inhibits intestinal P-glycoprotein (P-gp) expression in rats. In the present study, the effects of repeated pre-treatment with recombinant human INF-alpha (rhIFN-alpha) on oral and intravenous pharmacokinetics of a P-gp substrate, docetaxel (DTX; Taxotere) were investigated in a rat model. The bioavailability and distribution in different organs were also studied. Sprague-Dawley rats were subcutaneously pre-treated with either rhIFN-alpha for 8 days (4MIU kg(-1), once daily) or with pegylated-IFN-alpha (ViraferonPeg; 60 microg kg(-1), Days 1, 4 and 7). The rats were then distributed into sub-groups (n = 5-6) according to the pre-treatment type, and received one dose of [(14)C]DTX (20 mgkg(-1)) either orally or intravenously. Pharmacokinetics studies were then performed over 240 min, at the end of which tissues (intestine, liver, kidneys, lung, heart and brain) were immediately removed for radioactivity quantitation. Non-pegylated and pegylated IFN-alpha both increased DTX oral bioavailability parameters: C(max) (17.0+/-4.0 microg L(-1) (P < 0.02) and 18+/-5.5 microg L(-1) (P < 0.05), respectively, vs 7.4+/-2.5 microg L(-1) for the control) and AUC (0.036+/-0.010 microg h mL(-1) (P < 0.01) and 0.033+/-0.009 microg h mL(-1) (P < 0.01), respectively, versus 0.012+/-0.004 microg h mL(-1) for the control). IFN-alpha also delayed DTX absorption from 60 min in controls to about 95 min and 80 min in non-pegylated and pegylated treated animals, respectively. However, IFN-alpha did not affect intravenous DTX pharmacokinetics and it had a limited effect on tissue distribution at 240 min. [(14)C]DTX was decreased in intestine and enhanced in brain in both pre-treated groups. rhIFN-alpha modified the P-gp-dependent pharmacokinetics of DTX, limited its intestinal efflux and markedly enhanced its oral bioavailability.
- Published
- 2007
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46. Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.
- Author
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Teicher E, Vincent I, Bonhomme-Faivre L, Abbara C, Barrail A, Boissonnas A, Duclos-Vallée JC, Taburet AM, Samuel D, and Vittecoq D
- Subjects
- Adult, Aged, Alkynes, Area Under Curve, Benzoxazines blood, Benzoxazines pharmacokinetics, Benzoxazines therapeutic use, CD4 Lymphocyte Count, Cyclopropanes, Dose-Response Relationship, Drug, Female, Graft Rejection diagnosis, HIV drug effects, HIV Infections complications, Half-Life, Hepatitis C complications, Humans, Lopinavir, Male, Middle Aged, Nelfinavir blood, Nelfinavir pharmacokinetics, Nelfinavir therapeutic use, Pyrimidinones blood, Pyrimidinones pharmacokinetics, Pyrimidinones therapeutic use, Ritonavir blood, Ritonavir pharmacokinetics, Ritonavir therapeutic use, Tacrolimus blood, Tacrolimus therapeutic use, Viral Load methods, Antiretroviral Therapy, Highly Active, HIV Infections therapy, Hepatitis C therapy, Liver Transplantation, Tacrolimus pharmacokinetics
- Abstract
Objective: To characterise the interactions between tacrolimus and antiretroviral drug combinations in hepatitis C virus-HIV co-infected patients who had received a liver transplant., Design: An observational, open-label, multiple-dose, two-period, one-sequence design clinical trial in which patients received tacrolimus as an immunosuppressive therapy during the postoperative period and then had an antiretroviral drug regimen added. Tacrolimus pharmacokinetics were evaluated at steady state during these two periods., Methods: Fourteen patients participated in the study and seven participated in the intensified pharmacokinetic protocol. Patients were included if they had undergone liver transplantation for end-stage chronic hepatitis C, absence of opportunistic infection, a CD4 cell count of >150 cells/microL and an undetectable HIV plasma viral load (<50 copies/mL) under highly active antiretroviral therapy. During the posttransplantation period, the tacrolimus dose was adjusted according to blood concentrations. When liver function and the tacrolimus dose were stable, antiretroviral therapy was reintroduced., Results: When lopinavir/ritonavir were added to the tacrolimus regimen (seven patients), the tacrolimus dose was reduced by 99% to maintain the tacrolimus concentration within the therapeutic range. Only two patients were treated with nelfinavir, which led to a wide variation in inhibition of tacrolimus metabolism. When efavirenz (four patients) or a nucleoside analogue combination (one patient) was added, very little change in tacrolimus dosing was required., Conclusion: The lopinavir/ritonavir combination markedly inhibited tacrolimus metabolism, whereas the effect of efavirenz was small. Tacrolimus dosing must be optimised according to therapeutic drug monitoring and the antiretroviral drug combination.
- Published
- 2007
- Full Text
- View/download PDF
47. Development and validation of a method for the quantitation of Delta9 tetrahydrocannabinol in human plasma by high performance liquid chromatography after solid-phase extraction.
- Author
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Abbara C, Galy R, Benyamina A, Reynaud M, and Bonhomme-Faivre L
- Subjects
- Calibration, Humans, Reproducibility of Results, Sensitivity and Specificity, Spectrophotometry, Ultraviolet, Chromatography, High Pressure Liquid methods, Dronabinol blood
- Abstract
A high performance liquid chromatography (HPLC) procedure for the determination of Delta9 tetrahydrocannabinol (THC) in human plasma is described. A two-step solid-phase extraction on CN cartridges was coupled with a reversed phase HPLC system. THC was eluted using a mobile phase composed of methanol, acetonitrile and tetrabutylammonium perchlorate solution (0.005 M, pH 3.2), through a C18 Nucleosil column and detected at a wavelength of 215 nm. Calibration curve was linear over the range 5-100 ng/ml with a lower limit of quantification validated at 5 ng/ml. Extraction recovery using the developed extraction procedure was higher than 85%. This method is presently used for the quantification of THC in plasma samples from regular cannabis smokers.
- Published
- 2006
- Full Text
- View/download PDF
48. Recombinant interleukin-2 pre-treatment increases anti-tumor response to paclitaxel by affecting lung P-glycoprotein expression on the Lewis lung carcinoma.
- Author
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Hosten B, Challuau D, Gil S, Bouquet C, Marion S, Perricaudet M, Di Palma M, Farinotti R, and Bonhomme-Faivre L
- Subjects
- Administration, Oral, Animals, Blotting, Western, Carcinoma, Lewis Lung metabolism, Combined Modality Therapy, Female, Injections, Subcutaneous, Lung metabolism, Mice, Mice, Inbred C57BL, Recombinant Proteins therapeutic use, ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Antineoplastic Agents, Phytogenic administration & dosage, Carcinoma, Lewis Lung drug therapy, Interleukin-2 therapeutic use, Lung drug effects, Paclitaxel administration & dosage
- Abstract
The aim of the present study was to examine modifications of anti-tumor activity and toxicity of paclitaxel (PLX) when given p.o. after recombinant interleukin-2 (rIL-2) to Lewis lung carcinoma-bearing mice. PLX was given orally to mice at the dose of 15 mg/kg on day 8 and 30 mg/kg on day 15, either alone or after 16.5 microg of rIL-2 given i.p. twice a day either 1 or 3 days before. The anti-tumor activity was higher and PLX hematological toxicity not increased if orally administered PLX was given after a 3-day rIL-2 pre-treatment rather than if given alone. Lung metastasis was significantly lower and s.c. tumors were smaller in the PLX+rIL-2 group than in the PLX or rIL-2 or non-treated groups. In addition, a decrease in lung P-glycoprotein expression (investigated by Western blot analysis) was observed 1 h after the last administration of rIL-2 on day 7.
- Published
- 2006
- Full Text
- View/download PDF
49. Modification of the P-glycoprotein dependent pharmacokinetics of digoxin in rats by human recombinant interferon-alpha.
- Author
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Ben Reguiga M, Bonhomme-Faivre L, Orbach-Arbouys S, and Farinotti R
- Subjects
- Animals, Area Under Curve, Biological Availability, Blotting, Western, Dose-Response Relationship, Drug, Humans, Interferon alpha-2, Male, Rats, Rats, Sprague-Dawley, Recombinant Proteins, ATP Binding Cassette Transporter, Subfamily B, Member 1 physiology, Digoxin pharmacokinetics, Interferon-alpha pharmacology
- Abstract
Purpose: This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate., Methods: Human recombinant IFN-alpha was given to rats (n = 5-7 per group) daily for 8 days at different doses (IntronA) 10(6), 2.10(6), or 4.10(6) IU kg(-1), s.c.), whereas pegylated-IFN-alpha (ViraferonPeg), 29 microg kg(-1)) was given s.c. three times a week. Rats were then given digoxin (32 microg kg(-1)) i.v. or orally. The pharmacokinetics of digoxin was studied. Intestinal P-gp expression was also examined., Results: The pharmacokinetics of i.v. administered digoxin was not modified by IFN-alpha, but a dose-dependent increase in areas under the curve (AUCs) was observed in the orally administered digoxin parameters in rats (AUCs: 392 +/- 83 min microg L(-1), p < 0.01 and 550 +/- 97 min microg L(-1), p < 0.001, respectively, vs. 286 +/- 111 min microg L(-1) for control). A decrease in P-gp expression in the ileum (relative intensities: 0.70 +/- 0.19 for 4 Million International Unit (MIU) kg(-1) IFN-alpha-treated animals vs. 1.00 +/- 0.13 for controls, p < 0.05) and mainly in the jejunum (relative intensities: 0.46 +/- 0.13 for 4 MIU kg(-1) IFN-alpha-treated animals vs. 1.00 +/- 0.08 for controls, p < 0.001) was observed., Conclusion: IFN-alpha induces in vivo a significant dose-dependent inhibitory effect on intestinal P-gp activity related to a local decrease in its expression, thereby predicting important clinical consequences when IFN-alpha and other P-gp substrates are associated.
- Published
- 2005
- Full Text
- View/download PDF
50. Pharmacokinetics and neutrophil toxicity of paclitaxel orally administered in mice with recombinant interleukin-2.
- Author
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Jamois C, Comets E, Mentré F, Marion S, Farinotti R, and Bonhomme-Faivre L
- Subjects
- Administration, Oral, Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents, Phytogenic toxicity, Biological Availability, Interleukin-2 administration & dosage, Mice, Neutrophils, Paclitaxel toxicity, Antineoplastic Agents pharmacology, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Agents, Phytogenic pharmacokinetics, Interleukin-2 pharmacology, Paclitaxel administration & dosage, Paclitaxel pharmacokinetics
- Abstract
Purpose: Intrinsic P-glycoprotein (P-gp) expression in the gut limits paclitaxel uptake and, thus, its bioavailability when administered orally. Interleukin-2 has been reported to be a P-gp modulator in vitro and in vivo in mice. In the work described here, the effects of interleukin-2 pretreatment on pharmacokinetics and toxicity of paclitaxel orally administered were investigated., Methods: For the pharmacokinetic study, 96 mice were allocated to two groups receiving either 10 mg/kg of paclitaxel by the oral route alone or 16.5 microg of human recombinant interleukin-2 (rIL2) by the intraperitoneal route twice daily for 3 days and then paclitaxel. Pharmacokinetic profiles were analysed first by the Bailer method, and then using a compartmental approach. For the toxicity study, 90 Swiss mice were allocated to three groups receiving paclitaxel (10 mg/kg orally), rIL2 alone (16.5 microg i.p. twice daily for 3 days, control group), or both treatments. Haematological parameters were measured and the three groups were compared using the Bailer method. A Bonferroni correction was applied to the test., Results: A complex absorption of paclitaxel was revealed. The Bailer method showed that the mean area under the curve (AUC) values over 0-24 h were not significantly different in the two groups, despite a trend to reduced AUC in the pretreated group. The AUC over 0-0.5 h was significantly higher in the group pretreated with rIL2, but represented only a fraction of total exposure. These results were confirmed by the compartmental analysis. The elimination rate constant remained the same across both groups. rIL2 thus increased paclitaxel absorption for the 15 min following oral intake of the drug but did not enhance the overall exposure., Conclusion: We found that a 3-day pretreatment with rIL2 had some in vivo inhibitory effects on P-gp activity for a short period after oral dosing of paclitaxel. Those results encourage further investigation of the effect of rIL2 on the overall exposure of paclitaxel. On the other hand, it seems that the joint administration of the two drugs did not increase the risk of myelosuppression, which might be worth knowing to treat advanced cancers.
- Published
- 2005
- Full Text
- View/download PDF
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