The objective of the study was to determine the impact of food and different meal types on the pharmacokinetics of rilpivirine, a nonnucleoside reverse transcriptase inhibitor. In this open-label, randomized, crossover study, healthy volunteers received a single, oral 75 mg dose of rilpivirine either with a normal-fat breakfast (reference), under fasting conditions, with a high-fat breakfast, or with a protein-rich nutritional drink. Pharmacokinetic parameters were determined by non-compartmental methods and analyzed using a linear mixed-effects model. Safety was assessed throughout. The least-squares mean ratio for area under the plasma concentration-time curve to last timepoint was 0.57 (90% confidence interval [CI]: 0.46-0.72) under fasting conditions compared to dosing with a normal-fat breakfast. With a high-fat breakfast or only a protein-rich nutritional drink, the corresponding values were 0.92 (90% CI: 0.80-1.07) and 0.50 (90% CI: 0.41-0.61), respectively, compared to dosing with a normal-fat breakfast. Under all conditions, rilpivirine was generally safe and well tolerated. Administration of rilpivirine under fasting conditions or with only a protein-rich nutritional drink substantially lowered the oral bioavailability when compared to administration with a normal-fat breakfast. Rilpivirine bioavailability was similar when administered with a high-fat or normal-fat breakfast. Rilpivirine should always be taken with a meal to ensure adequate bioavailability.
Keywords: TMC278; food effect; nonnucleoside reverse transcriptase inhibitor; pharmacokinetics; rilpivirine.
© The Author(s) 2013.