Dataset Information

Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.

ABSTRACT: This open-label, fixed-sequence, phase 1 study evaluated the pharmacokinetic interaction between maraviroc (MVC) and ritonavir-boosted fosamprenavir (FPV/r) in healthy subjects. In period 1, subjects received 300 mg of MVC twice daily (BID; cohort 1) or once daily (QD; cohort 2) for 5 days. In period 2, cohort 1 subjects received 700/100 mg of FPV/r BID alone on days 1 to 10 and then FPV/r at 700/100 mg BID plus MVC at 300 mg BID on days 11 to 20; cohort 2 subjects received FPV/r at 1,400/100 mg QD alone on days 1 to 10 and then FPV/r at 1,400/100 mg QD plus MVC at 300 mg QD on days 11 to 20. Pharmacokinetic parameters, assessed on day 5 of period 1 and on days 10 and 20 of period 2, included the maximum plasma concentration (Cmax), the concentration at end of dosing interval (C?), and the area under the curve over dosing interval (AUC?). Safety and tolerability were also assessed. MVC geometric mean AUC?, Cmax, and C? were increased by 149, 52, and 374%, respectively, after BID dosing with FPV/r, and by 126, 45, and 80%, respectively, after QD dosing. Amprenavir (the active form of the prodrug fosamprenavir) and ritonavir exposures were decreased in the presence of MVC with amprenavir AUC?, Cmax, and C? decreased by 34 to 36% in the presence of FPV/r plus maraviroc BID and by 15 to 30% with FPV/r plus MVC QD both compared to FPV/r alone. The overall all-causality adverse-event (AE) incidence rate was 96.4%; all AEs were of mild or moderate severity. Commonly reported treatment-related AEs (>20% of patients overall) included diarrhea, fatigue, abdominal discomfort, headache, and nausea. No serious AEs or deaths occurred. In summary, maraviroc exposure increased in the presence of FPV/r, whereas MVC coadministration decreased amprenavir and ritonavir exposures. MVC dosed at 300 mg BID with FPV/r is not recommended due to concerns of lower amprenavir exposures; however, no dose adjustment is warranted with MVC at 150 mg BID in combination with FPV/r based on the available clinical data. MVC plus FPV/r was generally well tolerated; no new safety signals were detected.

SUBMITTER: Vourvahis M

PROVIDER: S-EPMC3837847 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.

Vourvahis Manoli M Plotka Anna A Mendes da Costa Laure L Fang Annie A Heera Jayvant J

Antimicrobial agents and chemotherapy 20130930 12

This open-label, fixed-sequence, phase 1 study evaluated the pharmacokinetic interaction between maraviroc (MVC) and ritonavir-boosted fosamprenavir (FPV/r) in healthy subjects. In period 1, subjects received 300 mg of MVC twice daily (BID; cohort 1) or once daily (QD; cohort 2) for 5 days. In period 2, cohort 1 subjects received 700/100 mg of FPV/r BID alone on days 1 to 10 and then FPV/r at 700/100 mg BID plus MVC at 300 mg BID on days 11 to 20; cohort 2 subjects received FPV/r at 1,400/100 mg ...[more]

PMID: 24080663

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Dataset Information

Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.

Publications

Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.

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