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Titolo:
Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers
Autore:
Khaliq, Y; Gallicano, K; Tisdale, C; Carignan, G; Cooper, C; McCarthy, A;
Indirizzi:
Ottawa Hosp, Clin Invest Unit, Ottawa, ON, Canada Ottawa Hosp Ottawa ON Canada Hosp, Clin Invest Unit, Ottawa, ON, Canada Ottawa Hosp, Dept Pharm, Ottawa, ON, Canada Ottawa Hosp Ottawa ON CanadaOttawa Hosp, Dept Pharm, Ottawa, ON, Canada Ottawa Hosp, Dept Med, Ottawa, ON, Canada Ottawa Hosp Ottawa ON CanadaOttawa Hosp, Dept Med, Ottawa, ON, Canada Ottawa Hosp, Ottawa Hosp Res Inst, Ottawa, ON, Canada Ottawa Hosp Ottawa ON Canada p, Ottawa Hosp Res Inst, Ottawa, ON, Canada
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 6, volume: 51, anno: 2001,
pagine: 591 - 600
SICI:
0306-5251(200106)51:6<591:PIBMAR>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ERYTHROMYCIN BREATH TEST; P-GLYCOPROTEIN; PLASMODIUM-FALCIPARUM; LIVER; MODULATION; INVITRO; DRUGS; ASSAY;
Keywords:
cytochrome P450 3A4; erythromycin breath test; mefloquine; pharmacokinetic interaction; ritonavir;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Gallicano, K Axelson Biopharma Res Inc, Suite 309,2083 Alma St, Vancouver,BC V6R 4N6, Canada Axelson Biopharma Res Inc Suite 309,2083 Alma St Vancouver BC Canada V6R 4N6
Citazione:
Y. Khaliq et al., "Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers", BR J CL PH, 51(6), 2001, pp. 591-600

Abstract

Aims To evaluate the pharmacokinetic interaction between ritonavir and mefloquine. Methods Healthy volunteers participated in two separate, nonfasted, three-treatment, three-period, longitudinal phramacokinetic 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 3 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 3 weeks, ritonavir single dose repeated 3 days after the last mefloquine dose. Erythromycin breath test (ERMBT) was administered with and without drug treatments in study 2. Results 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 (C-max) 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(0,12h) by 31%, C-max by 36%, and predose levels by 43%, and did not affect ritonavir binding to plasma proteins. Study 2. Mefloquine did not alter single-doss ritonavir pharmacokinetics. Less than 8% changes in AUC and C-max were observed with high variability (90%CIs: -26% to -45%). Mefloquine had no effect on the ERMBT whereas ritonavir decreased activity by 98%. Conclusions 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 09:06:29