Impact of Food and Different Meal Types on the Pharmacokinetics of Rilpivirine

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.