title: Impact of food and different meal types on the pharmacokinetics of rilpivirine.
abstract: 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.
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. hcrauwel@its.jnj.com
authors.forename: Herta M
authors.initials: HM
authors.lastname: Crauwels
authors.forename: Rolf P G
authors.initials: RP
authors.lastname: van Heeswijk
authors.forename: Annemie
authors.initials: A
authors.lastname: Buelens
authors.forename: Marita
authors.initials: M
authors.lastname: Stevens
authors.forename: Katia
authors.initials: K
authors.lastname: Boven
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D062408:Breakfast; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D019422:Dietary Sucrose; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005526:Food, Formulated; D018565:Food-Drug Interactions; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D062407:Meals; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011506:Proteins / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068696:Rilpivirine; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D019422:Dietary Sucrose; D009570:Nitriles; D011506:Proteins; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C082131:Ensure formulated food; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine
keywords: TMC278; food effect; nonnucleoside reverse transcriptase inhibitor; pharmacokinetics; rilpivirine