5 results on '"Fielding, Anitra"'
Search Results
2. Pharmacokinetics and Safety of Olaparib in Patients with Advanced Solid Tumours and Renal Impairment
- Author
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Rolfo, Christian, de Vos-Geelen, Judith, Isambert, Nicolas, Molife, L Rhoda, Schellens, Jan H M, De Grève, Jacques, Dirix, Luc, Grundtvig-Sørensen, Peter, Jerusalem, Guy, Leunen, Karin, Mau-Sørensen, Morten, Plummer, Ruth, Learoyd, Maria, Bannister, Wendy, Fielding, Anitra, Ravaud, Alain, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Clinical sciences, Medical Genetics, Laboratory for Medical and Molecular Oncology, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
- Subjects
Adult ,Male ,medicine.medical_specialty ,PHARMACOKINETICS ,No-observed-adverse-effect level ,Metabolic Clearance Rate ,Urology ,Renal function ,Administration, Oral ,Poly(ADP-ribose) Polymerase Inhibitors ,Kidney ,olaparib ,Piperazines ,Olaparib ,03 medical and health sciences ,chemistry.chemical_compound ,polymerase inhibitor ,0302 clinical medicine ,Pharmacokinetics ,Neoplasms ,Medicine ,Advanced Solid Tumours ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Dosing ,Renal Insufficiency ,Renal impairment ,Aged ,Pharmacology ,Medicine(all) ,No-Observed-Adverse-Effect Level ,business.industry ,Area under the curve ,INHIBITOR ,Middle Aged ,CANCER ,Confidence interval ,chemistry ,Tolerability ,030220 oncology & carcinogenesis ,Phthalazines ,Female ,Safety ,business - Abstract
BACKGROUND: Olaparib, a potent oral poly(ADP-ribose) polymerase inhibitor, is partially renally cleared. We investigated the pharmacokinetics and safety of olaparib in patients with mild or moderate renal impairment to provide dosing recommendations. METHODS: This phase I open-label study assessed the pharmacokinetics, safety and tolerability of single-dose, oral 300-mg olaparib tablets in adults (aged 18-75 years) with solid tumours. Patients had normal renal function, or mild or moderate renal impairment (estimated creatinine clearance ≥ 81, 51-80 or 31-50 mL/min, respectively). Blood was collected for 96 h, and urine samples collected for 24 h post-dose. Patients could continue taking olaparib 300 mg twice daily for a long-term safety assessment. RESULTS: Overall, 44 patients received one or more doses of olaparib and 38 were included in the pharmacokinetic assessment. Patients with mild renal impairment had an area under the curve geometric least-squares mean ratio of 1.24 (90% confidence interval 1.06-1.47) and a geometric least-squares mean maximum plasma concentration ratio of 1.15 (90% confidence interval 1.04-1.27) vs. those with normal renal function. In patients with moderate renal impairment, the geometric least-squares mean ratio for the area under the curve was 1.44 (90% confidence interval 1.10-1.89) and for the maximum plasma concentration was 1.26 (90% confidence interval 1.06-1.48) vs. those with normal renal function. No new safety signals were detected in patients with mild or moderate renal impairment. CONCLUSIONS: In patients with mild renal impairment, the small increase in exposure to olaparib was not considered clinically relevant. In patients with moderate renal impairment, exposure to olaparib increased by 44%; thus, these patients should be carefully monitored and the tablet dose should be adjusted to 200 mg twice daily. CLINICAL TRIALS REGISTRATION: NCT01894256.
- Published
- 2019
3. Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours.
- Author
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Plummer, Ruth, Swaisland, Helen, Leunen, Karin, Herpen, Carla, Jerusalem, Guy, Grève, Jacques, Lolkema, Martijn, Soetekouw, Patricia, Mau-Sørensen, Morten, Nielsen, Dorte, Spicer, James, Fielding, Anitra, So, Karen, Bannister, Wendy, Molife, L. Rhoda, van Herpen, Carla M L, De Grève, Jacques, Lolkema, Martijn P, and Mau-Sørensen, Morten
- Subjects
DRUG tablets ,DRUG formularies ,ORAL medication ,PHARMACOKINETICS ,BRCA genes ,GENETIC mutation ,CANCER patients ,ANTINEOPLASTIC agents ,BIOTRANSFORMATION (Metabolism) ,CLINICAL trials ,COMPARATIVE studies ,CROSSOVER trials ,DIET ,DRUG-food interactions ,DRUG administration ,HETEROCYCLIC compounds ,INTESTINAL absorption ,RESEARCH methodology ,MEDICAL cooperation ,METASTASIS ,PHARMACEUTICAL chemistry ,RESEARCH ,RESEARCH funding ,TIME ,TUMORS ,EVALUATION research - Abstract
Background: The oral PARP inhibitor olaparib has shown efficacy in patients with BRCA-mutated cancer. This Phase I, open-label, three-part study (Parts A-C) in patients with advanced solid tumours evaluated the effect of food on the pharmacokinetics (PK) of olaparib when administered in tablet formulation.Methods: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part C, patients were allowed continued access to olaparib. Safety was assessed throughout, with data reported for Parts A and B.Results: A total of 60 and 56 patients were evaluable for safety and PK analyses, respectively; 57 patients entered Part B. Rate of olaparib absorption was slower in the presence of food (t max delayed by 2.5 h), resulting in a statistically significant ~21 % decrease in peak plasma exposure (C max) [ratio of geometric means (90 % CI), 0.79 (0.72, 0.86)] but only a marginal increase in olaparib absorption (AUC0-∞) [ratio of geometric means (90 % CI), 1.08 (1.01, 1.16)]. The point estimate and 90 % CI for the AUC0-∞ treatment ratio were within pre-defined bioequivalence limits (0.80-1.25). Adverse event data were consistent with the known safety profile of olaparib.Conclusions: Results of this study showed that a high-fat meal decreases the rate of absorption and peak exposure to olaparib 300 mg tablets, although in the absence of an effect on the extent of olaparib absorption. [ABSTRACT FROM AUTHOR]- Published
- 2015
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4. Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration.
- Author
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Purkins, Lynn, Wood, Nolan, Ghahramani, Parviz, Love, Edward R., Eve, Malcolm D., and Fielding, Anitra
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TRIAZOLES ,ANTIFUNGAL agents ,PHENYTOIN ,ANTICONVULSANTS ,PHARMACOKINETICS ,PHARMACOLOGY - Abstract
Voriconazole is a new triazole antifungal agent, and is metabolized by the cytochrome P450 isoenzymes CYP2C9, CYP2C19, and, to a lesser extent, by CYP3A4. Phenytoin is an inducer of CYP3A4 activity, and a substrate and inducer of CYP2C9 and CYP2C19. The present studies investigated the pharmacokinetic interactions of voriconazole and phenytoin when coadministered. Two placebo-controlled parallel-group studies were conducted in healthy male volunteers. Study A was an open-label study and investigated the effect of phenytoin (300 mg once daily) on the steady-state pharmacokinetics of voriconazole (200 mg and 400 mg twice daily). Study B was a double-blind randomized study to investigate the effects of voriconazole (400 mg twice daily) on the steady-state pharmacokinetics of phenytoin (300 mg once daily). C
max and AUCτ were compared at days 7, 21, and 28 (Study A), and at days 7 and 17 (Study B). All adverse events were recorded. Study A: 21 subjects were evaluable (10 voriconazole + phenytoin, 11 voriconazole + placebo). For subjects receiving voriconazole (200 mg twice daily) plus phenytoin, the day 21/day 7 ratios for voriconazole Cmax and AUCτ were 60.7%[90% confidence interval (CI) 50.1, 73.6] and 35.9% (90% CI 29.7, 43.3), respectively. Adjusted for voriconazole + placebo, the ratios between the means were 50.7% (90% CI 38.8, 66.1) and 30.6% (90% CI 23.5, 39.7), respectively. When the dose of voriconazole was increased to 400 mg twice daily, the day 28/day 7 ratios for voriconazole Cmax and AUCτ were 134% (90% CI 89.2, 200) and 139% (90% CI 97.3, 199), respectively. Study B: 15 subjects were evaluable for pharmacokinetic assessments (six phenytoin + voriconazole, nine phenytoin + placebo). The ratios between the means for phenytoin + voriconazole/phenytoin + placebo on day 17 vs. day 7 were: phenytoin Cmax 167% (90% CI 144, 193) and phenytoin AUCτ 181% (90% CI 156, 210). All treatments were well tolerated: most adverse events were mild/moderate and transient. Repeat dose administration of phenytoin decreased the mean steady-state Cmax and AUCτ of voriconazole by approximately 50% and 70%, respectively. Increasing the dose of voriconazole from 200 mg to 400 mg b.d. compensated for this effect. Repeat dose administration of 400 mg b.d. voriconazole increased the mean steady-state Cmax and AUCτ of phenytoin by approximately 70% and 80%, respectively. It is therefore recommended that plasma phenytoin concentrations are monitored and the dose adjusted as appropriate when phenytoin is coadministered with voriconazole. [ABSTRACT FROM AUTHOR]- Published
- 2003
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5. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir.
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Muirhead, Gary J., Wulff, Maria B., Fielding, Anitra, Kleinermans, Diane, and Burns, Niel
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PROTEASE inhibitors ,SILDENAFIL ,PHARMACOKINETICS - Abstract
Investigates the effect of the antiretroviral protease inhibitors saquinovir and ritonavir on the pharmacokinetic properties and tolerability of sildenafil. Effect of sildenafil on the steady-state pharmacokinetics of saquinovir and ritonavir; Indication that both saquinovir and ritonavir modify the pharmacokinetics of sildenafil presumably through inhibition of cytochrome P450 3A4.
- Published
- 2000
- Full Text
- View/download PDF
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