title: Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers.
abstract: 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.
authors: Tibotec, Inc, 1020 Stony Hill Road, Yardley, PA 19067, USA. vsekar@tibus.jnj.com
authors: Vanitha J
authors: VJ
authors: Sekar
authors: Sabrina
authors: S
authors: Spinosa-Guzman
authors: Els
authors: E
authors: De Paepe
authors: Martine
authors: M
authors: De Pauw
authors: Tony
authors: T
authors: Vangeneugden
authors: Eric
authors: E
authors: Lefebvre
authors: Richard M W
authors: RM
authors: Hoetelmans
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D000069454:Darunavir; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C056228:14-hydroxyclarithromycin; D017291:Clarithromycin; D019438:Ritonavir; D000069454:Darunavir