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Darunavir/Ritonavir Pharmacokinetics Following Coadministration With Clarithromycin in Healthy Volunteers
Author(s) -
Sekar Vanith J.,
SpinosaGuzman Sabrina,
Paepe El D.,
Pauw Martin D.,
Vangeneugden Tony,
Lefebvre Eric,
Hoetelmans Richar M. W.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007309706
Subject(s) - darunavir , ritonavir , clarithromycin , pharmacokinetics , pharmacology , crossover study , tolerability , drug interaction , medicine , adverse effect , human immunodeficiency virus (hiv) , viral load , virology , antiretroviral therapy , helicobacter pylori , placebo , alternative medicine , pathology
This study investigated the steady‐state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low‐dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV‐negative healthy volunteers. In a 3‐way crossover study, 18 individuals received darunavir/ritonavir 400/100 mg bid, clarithromycin 500 mg bid, and darunavir/ritonavir 400/100 mg bid plus clarithromycin 500 mg bid in 3 separate sessions for 7 days, with a washout period of at least 7 days between treatments. Pharmacokinetic assessment was performed on day 7. Safety and tolerability of the study medication were monitored throughout. Coadministration of darunavir/ritonavir with clarithromycin resulted in a reduction in darunavir maximum plasma concentration (C max ) and area under the curve from administration until 12 hours postdose (AUC 12 h ) of 17% and 13%, respectively. Ritonavir C max and AUC 12 h were unchanged. During coadministration with darunavir/ritonavir, clarithromycin C max and AUC 12 h increased by 26% and 57%, respectively; 14‐hydroxy‐clarithromycin plasma concentrations were reduced to below the lower limit of quantification (<50 ng/mL). The study medication was generally well tolerated. Based on these pharmacokinetic findings, neither clarithromycin nor darunavir/ritonavir dose adjustments are necessary when clarithromycin is coadministered with darunavir/ritonavir.