Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers

• Published in: Journal of clinical pharmacology Vol. 48; no. 1; p. 60
• Main Authors: Sekar, Vanitha J, Spinosa-Guzman, Sabrina, De Paepe, Els, De Pauw, Martine, Vangeneugden, Tony, Lefebvre, Eric, Hoetelmans, Richard M W
• Format: Journal Article
• Language: English
• Published: England 01.01.2008
• Subjects: Adolescent; Adult; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacokinetics; Area Under Curve; Chromatography, High Pressure Liquid; Clarithromycin - analogs & derivatives; Clarithromycin - blood; Clarithromycin - metabolism; Clarithromycin - pharmacokinetics; Cross-Over Studies; Darunavir; Dose-Response Relationship, Drug; Drug Combinations; Female; HIV Protease Inhibitors - blood; HIV Protease Inhibitors - pharmacokinetics; Humans; Male; Middle Aged; Ritonavir - blood; Ritonavir - pharmacokinetics; Sulfonamides - blood; Sulfonamides - pharmacokinetics; Time Factors
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270007309706

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 (Cmax) and area under the curve from administration until 12 hours postdose (AUC12 h) of 17% and 13%, respectively. Ritonavir Cmax and AUC12 h were unchanged. During coadministration with darunavir/ritonavir, clarithromycin Cmax and AUC12 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.