Single- and multiple-dose pharmacokinetics of etravirine administered as two different formulations in HIV-1-infected patients

Background An open-label, randomized, crossover study to evaluate the pharmacokinetics of two different formulations of etravirine after single and multiple dosing. Methods Treatment-experienced HIV-1-infected patients with viral load <50 copies/ml continued their current antiretroviral regimen and added etravirine twice daily for 7 days with a morning intake on day 8. Etravirine was administered following food as either 800 mg twice daily of the Phase II formulation or 100 mg or 200 mg twice daily of the Phase III formulation. A 12 h pharmacokinetic assessment was performed on days 1 and 8. Results After single- and multiple-dose administration, the exposure to etravirine was lower with 100 mg twice daily and higher with 200 mg twice daily compared with 800 mg twice daily. On day 8, the mean (±sd) area under the plasma concentration-time curve over 12 h (AUC 0–12 h ) was 1,284 (±958) ng•h/ml when etravirine was administered as 100 mg twice daily ( n=33), 3,713 (±2,069) ng•h/ml when administered as 200 mg twice daily ( n=27) and 2,607 (±2,135) ng•h/ml when administered as 800 mg twice daily ( n=32). Both formulations and all doses of etravirine tested were generally safe and well tolerated. Conclusions The range of exposure to etravirine was comparable between 200 mg twice daily dose and 800 mg twice daily. The Phase III formulation of etravirine significantly improves the bioavailability of etravirine over the Phase II formulation with reduced interpatient variability in etravirine pharmacokinetics.