Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers
| Autor: | Y, Khaliq, K, Gallicano, C, Tisdale, G, Carignan, C, Cooper, A, McCarthy |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Ritonavir Time Factors Adolescent Metabolic Clearance Rate Administration Oral HIV Protease Inhibitors Middle Aged Models Biological Mixed Function Oxygenases Mefloquine Antimalarials Breath Tests Cytochrome P-450 Enzyme System Area Under Curve Cytochrome P-450 CYP3A Humans Drug Interactions Female Chromatography High Pressure Liquid |
| Zdroj: | British journal of clinical pharmacology. 51(6) |
| ISSN: | 0306-5251 |
| Popis: | To evaluate the pharmacokinetic interaction between ritonavir and mefloquine.Healthy volunteers participated in two separate, nonfasted, three-treatment, three-period, longitudinal pharmacokinetic studies. Study 1 (12 completed): ritonavir 200 mg twice daily for 7 days, 7 day washout, mefloquine 250 mg once daily for 3 days then once weekly for 4 weeks, ritonavir restarted for 7 days simultaneously with the last mefloquine dose. Study 2 (11 completed): ritonavir 200 mg single dose, mefloquine 250 mg once daily for 3 days then once weekly for 2 weeks, ritonavir single dose repeated 2 days after the last mefloquine dose. Erythromycin breath test (ERMBT) was administered with and without drug treatments in study 2.Study 1: Ritonavir caused less than 7% changes with high precision (90% CIs: -12% to 11%) in overall plasma exposure (AUC(0,168 h)) and peak concentration (Cmax) of mefloquine, its two enantiomers, and carboxylic acid metabolite, and in the metabolite/mefloquine and enantiomeric AUC ratios. Mefloquine significantly decreased steady-state ritonavir plasma AUC(0,12 h) by 31%, Cmax by 36%, and predose levels by 43%, and did not affect ritonavir binding to plasma proteins. Study 2: Mefloquine did not alter single-dose ritonavir pharmacokinetics. Less than 8% changes in AUC and Cmax were observed with high variability (90%CIs: -26% to 45%). Mefloquine had no effect on the ERMBT whereas ritonavir decreased activity by 98%.Ritonavir minimally affected mefloquine pharmacokinetics despite strong inhibition of CYP3A4 activity from a single 200 mg dose. Mefloquine had variable effects on ritonavir pharmacokinetics that were not explained by hepatic CYP3A4 activity or ritonavir protein binding. |
| Databáze: | OpenAIRE |
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