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283 results on '"Houin, Georges"'

4. Is once-daily mesalazine equivalent to the currently used twice-daily regimen? A study performed in 30 healthy volunteers

Author

Gandia, Peggy, Idier, Isabelle, and Houin, Georges

Subjects
Pharmacokinetics -- Analysis, Mesalamine -- Dosage and administration -- Complications and side effects, Health, Analysis, Complications and side effects, Dosage and administration
Abstract

A randomized, 2-way, crossover study was conducted in 30 volunteers to compare the pharmacokinetic profile of a new once-daily dosing regimen of mesalazine (1 x 4 g/d) with the current [...]

Published
2007

6. Influence of simulated weightlessness on the intramuscular and oral pharmacokinetics of promethazine in 12 human volunteers

Author

Gandia, Peggy, Saivin, Sylvie, Le-Traon, Anne Pavy, Guell, Antonio, and Houin, Georges

Subjects
Promethazine -- Dosage and administration -- Research, Motion sickness -- Drug therapy -- Research -- Risk factors, Weightlessness -- Risk factors -- Research, Health, Drug therapy, Research, Risk factors, Dosage and administration
Abstract

The National Aeronautics and Space Administration (NASA) recommends using promethazine to prevent and treat space motion sickness, but pharmacologic responses in space and on Earth are different. Twelve volunteers were [...]

Published
2006

28. Prediction of carboplatin clearance from standard morphological and biological patient characteristics

Author

Chatelut, Etienne, Canal, Pierre, Brunner, Valerie, Chevreau, Christine, Pujol, Andre, Boneu, Andree, Roche, Henri, Houin, Georges, and Bugat, Roland

Subjects
Carboplatin -- Physiological aspects, Antineoplastic agents -- Evaluation, Health
Abstract

Background. Hematologic toxicity of an antineoplastic drug, carboplatin, is largely dependent on its pharmacokinetics. Its therapeutic efficacy may be related to plasma drug exposure. Dosage adjustment based on isotopic determination of glomerular filtration rate has been proposed, but its ambulatory use is not yet conceivable. The dosage adjustment based on a patient's creatinine clearance relies on accurate measurement of urine volume per unit time and can be done with ease. Purpose: A population pharmacokinetics study was undertaken to determine a relationship between carboplatin clearance and patient characteristics. A predictive formula was derived that was then prospectively evaluated, and its outcome was compared with that obtained by other methods available to predict carboplatin clearance. Methods: Plasma carboplatin pharmacokinetics determined as ultrafilterable platinum in 70 patients (age range, 23-84 years) treated with different combination regimens that included carboplatin at doses ranging from 184 mg to 950 mg (1-hour intravenous infusion) for various tumor types. Data were analyzed using the nonlinear mixed effects model (NONMEM). The data from 34 patients (46 cycles) were utilized to derive the most predictive formula. The reliability of the formula was subsequently evaluated by analyzing the data obtained from 36 other patients (43 cycles). Results: Carboplatin clearance (mL/min) was found to be best predicted by the following formula: 0.134 . weight + [218 . weight . (1 - 0.00457 . age) . (1 - 0.314 . sex)]/creatinine expressed in micromolar concentration (with weight in kg, age in years, and sex = 0 if male and sex = 1 if female). Prospectively, this formula predicted the carboplatin clearance with good precision (median absolute percent error of 10% [range, 0% to 30%]) and minimal bias (median percent error of 2% [range, -25% to 30%]). This method of prediction was as accurate as the one derived from the measurement of glomerular filtration rate following the injection of 51 chromium-EDTA. Conclusion: This formula for the determination of carboplatin clearance can permit individualized determination of carboplatin dosage in adults by simply multiplying the calculated carboplatin clearance by the area under the curve for the desired dosage administration.

Published
1995

34. A whole-body physiologically based pharmacokinetic (WB-PBPK) model of ciprofloxacin : a step towards predicting bacterial killing at sites of infection.

Author

Sadiq, Muhammad W, Nielsen, Elisabet I., Khachman, Dalia, Conil, Jean-Marie, Georges, Bernard, Houin, Georges, Laffont, Celine M, Karlsson, Mats O., Friberg, Lena E., Sadiq, Muhammad W, Nielsen, Elisabet I., Khachman, Dalia, Conil, Jean-Marie, Georges, Bernard, Houin, Georges, Laffont, Celine M, Karlsson, Mats O., and Friberg, Lena E.

Abstract

The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model was built using a non-linear mixed effects approach based on data from 102 adult intensive care unit patients. Tissue to plasma distribution coefficients (Kp) were available from the literature and used as informative priors. The developed WB-PBPK model successfully characterized both the typical trends and variability of the available ciprofloxacin plasma concentration data. The WB-PBPK model was thereafter combined with a pharmacokinetic-pharmacodynamic (PKPD) model, developed based on in vitro time-kill data of ciprofloxacin and Escherichia coli to illustrate the potential of this type of approach to predict the time-course of bacterial killing at different sites of infection. The predicted unbound concentration-time profile in extracellular tissue was driving the bacterial killing in the PKPD model and the rate and extent of take-over of mutant bacteria in different tissues were explored. The bacterial killing was predicted to be most efficient in lung and kidney, which correspond well to ciprofloxacin's indications pneumonia and urinary tract infections. Furthermore, a function based on available information on bacterial killing by the immune system in vivo was incorporated. This work demonstrates the development and application of a WB-PBPK-PD model to compare killing of bacteria with different antibiotic susceptibility, of value for drug development and the optimal use of antibiotics.

Published
2017
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39. Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations

Author

Georges, Bernard, Conil, Jean-Marie, Ruiz, Stéphanie, Seguin, Thierry, Cougot, Pierre, Fourcade, Olivier, Houin, Georges, and Saivin, Sylvie

Subjects
Critical Care, Dose-Response Relationship, Drug, Pharmacokinetic Dynamic Relationships, Microbial Sensitivity Tests, Ceftazidime, Models, Biological, Respiration, Artificial, Anti-Bacterial Agents, Intensive Care Units, Pneumonia, Bacterial, Humans, Computer Simulation, Pseudomonas Infections, Monte Carlo Method, Glomerular Filtration Rate
Abstract

The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations. The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases.Our results propose individual therapeutic drug monitoring taking into account: For the patient: the reason of admission in the ICU, the mechanical ventilation status and the creatinine clearance calculated by the modified diet in renal disease (MDRD). • For the antibiotics: the lung distribution, the minimal inhibitory concentration (MIC) of the strain to eradicate and the potential toxicity. AIM To predict the ceftazidime dosage regimen as a function of the glomerular filtration rate expressed by the modification of the diet in renal disease (MDRD), reason for admission and mechanical ventilation in intensive care unit (ICU) patients to treat Pseudomonas aeruginosa pneumonia.A published and qualified population pharmacokinetic model was used to perform Monte Carlo simulations of ceftazidime concentrations. The serum target of 40-100 mg l(-1) was defined based on the minimal inhibitory concentration (MIC), the European break point (EBP), the pulmonary drug diffusion and toxicity. The recommended dosage regimens were based on the maximum percentile of the patients with simulated steady state concentrations reaching the target.Steady-state was reached at 72 h whatever the MDRD. The simulations of serum concentrations generated higher percentiles of the population reaching the target after continuous administration. We recommend a 4 g continuous dose after the usual 2 g loading dose for patients with MDRD from 10 to 30 ml min(-1) , 6 g for MDRD between 40 and 80 ml min(-1) , 8 g for MDRD from 90 to 110 ml min(-1) , 10 g for MDRD from 120 to 190 ml min(-1) and 12 g day(-1) for patients with MDRD higher than 200 ml min(-1) .Our study demonstrated that in ICU patients for a given MDRD, steady-state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.

Published
2011

40. Optimising ciprofloxacin dosing in intensive care patients based on pharmacodynamic target attainment

Author

Khachman, Dalia, Conil, Jean-Marie, Georges, Bernard, Saivin, Sylvie, Houin, Georges, Toutain, Pierre-Louis, Institut National de la Recherche Agronomique (INRA), Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Purpan (CHU Purpan), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Saisissez le nom du laboratoire, du service ou du département., Ville service., and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

42. Pharmacokinetics, metabolism and excretion of megazol in a Trypanosoma brucei gambiense primate model of human African trypanosomiasis - Preliminary study

Author

Enanga, Bertin, Ndong, Jerôme Mezui Me, Boudra, Hamid, Debrauwer, Laurent, Dubreuil, Guy, Bouteille, Bernard, Chauviere, Gérard, Labat, Christian, Dumas, Michel, Perie, Jacques, Houin, Georges, Faculte des Sciences Pharmaceutiques, Centre International de Recherches Médicales de Franceville (CIRMF), Xénobiotiques, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut d'Epidémiologie Neurologique et de Neurologie Tropicale, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
suramin, mice, [SDV]Life Sciences [q-bio], Megazol, Pharmacokinetics, Trypanosoma brucei, gambiense
Abstract

International audience; The pharmacokinetics of megazol (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, CAS 19622-55-0) was investigated after a 100 mg/kg oral administration to six primates infected with Trypanosoma brucei gambiense. The plasma levels of megazol were between 0.2 mu g/ml and 46 mu g/ml 24 h after dosing in all animals. In animals with prolonged infection, megazol absorption was accelerated (T-max was 4 h compared with 8 h, for day 53 and day 39 post inoculation) but the amount absorbed was not modified. The megazol concentrations in the cerebrospinal fluid represented between 5.5 % and 10.6 %, of the plasma levels at the same rimes. Unchanged megazol was eliminated predominantly via the kidneys: 46-96 % of the ingested dose was recovered in the urine, compared with 0-5 % in the faeces. Furthermore, this urinary elimination of megazol was altered in animals with prolonged infections. In the urine, 4 unknown metabolites were observed, unchanged megazol was characterized by LC-MS/MS. This study indicates that megazol crosses the blood-brain barrier after oral administration. Prolonged infections affect the absorption of megazol and its urinary elimination.

Published
2000

43. Pharmacokinetics, Metabolism and Excretion of Megazol in a Trypanosoma brucei gambiense Primate Model of Human African Trypanosomiasis

Author

Enanga, Bertin, additional, Ndong, Jerôme, additional, Boudra, Hamid, additional, Debrauwer, Laurent, additional, Dubreuil, Guy, additional, Bouteille, Bernard, additional, Chauvière, Gérard, additional, Labat, Christian, additional, Dumas, Michel, additional, Périé, Jacques, additional, and Houin, Georges, additional

Published
2011
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