Lack of effect of efavirenz on the pharmacokinetics of tipranavir/ritonavir (TPV/r) in healthy volunteers. Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] Journal article

Previously it has been shown that TPV/r does not affect efavirenz (EFV) plasma concentrations. This study investigates the effect of steady-state EFV on steady-state TPV/r pharmacokinetics. This was a single center, open-label, multiple-dose study in healthy adult female and male volunteers. TPV/r 500/200 mg BID was given with food for 24 days. After dosing with TPV/r for 10 days, EFV 600 mg QD was added to the regimen. Intensive pharmacokinetic (PK) sampling was done on days 10 and 24. Validated bioanalytical HPLC-MS/MS methods were used to determine plasma TPV, ritonavir (RTV) and EFV concentrations. Thirty-four subjects were entered into the study and 16 subjects completed it. The geometric mean ratio (GMR) and 90% confidence intervals (90% CI) for TPV and RTV area under the curve (AUC), Cmax and Cmin comparing TPV/r alone and in combination with EFV were: 0.97 (0.87-1.09), 0.92 (0.81-1.03) and 1.19 (0.93-1.54) for TPV, and 1.03 (0.78-1.38), 0.92 (0.65-1.30) and 1.04 (0.72-1.48) for RTV. Frequently observed AEs were diarrhea, headache, dizziness, abnormal dreams and rash. EFV had no effect on the steady-state PK of TPV or RTV, with the exception of a 19% increase in TPV Cmin which is not clinically relevant. TPV/r can be safely co-administered with EFV and without the need for a dose adjustment.

Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother]