Steady-State Pharmacokinetics of Emtricitabine and Tenofovir Disoproxil Fumarate Administered Alone and in Combination in Healthy Volunteers

The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, were considered good candidates for a fixed‐dose combination product that could be administered as a single pill once daily (qd), thereby simplifying existing treatment regimens and promoting patient adherence. As both drugs are extensively renally eliminated, a randomized, 3‐way crossover study was conducted in 19 healthy volunteers to formally evaluate the potential pharmacokinetic interaction when the drugs are administered alone and together (ie, 200 mg emtricitabine qd for 7 days, 300 mg tenofovir disoproxil fumarate qd for 7 days, and 200 mg emtricitabine plus 300 mg tenofovir disoproxil fumarate qd for 7 days) with no washout between treatments. Steady‐state pharmacokinetic parameters (AUCτ, Cmax, and Cmin) of emtricitabine and tenofovir (as tenofovir disoproxil fumarate) in combination were essentially equivalent versus each drug alone, providing a pharmacokinetic rationale for combining these products in emtricitabine/tenofovir disoproxil fumarate fixed‐dose tablets.