Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers

Background This open-label, crossover study investigated the pharmacokinetic interaction between TMC114 (darunavir [Prezista™]), administered with low-dose ritonavir (TMC114/r) and efavirenz (EFV) in HIV-negative, healthy volunteers. Methods Volunteers received TMC114/r 300/100 mg twice daily for 6 days, and once daily on day 7 (session 1). After a 7-day washout period volunteers received EFV 600 mg once daily for 18 days (session 2), with coadministration of TMC114/r 300/100 mg twice daily from day 11–day 16 and TMC114/r once daily on day 17. Results When coadministered with TMC114/r, plasma concentrations of EFV were slightly increased. In the presence of TMC114/r, EFV minimum (C min ) and maximum (C max ) plasma concentrations increased by 15–17%, and by 21% for EFV area under the curve (AUC 24h ). TMC114/r and EFV coadministration resulted in TMC114 C min , C max and AUC 12h decreases of 31%, 15% and 13%, respectively. No serious adverse events (AEs) or AEs leading to withdrawal were reported in this trial. Overall, TMC114/r and EFV coadministration was well tolerated. Conclusions The clinical significance of the changes in AUC and C min seen with TMC114/r and EFV coadministration has not been established; this combination should be used with caution. Similar findings are expected with the approved TMC114/r 600/100 mg twice daily dose.