Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective Two open-label, randomized, cross-over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate. Methods Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co-administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h. Results The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC12 h) for etravirine co-administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC24 h was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2. Conclusions These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co-administered.