title: Evaluation of the effects of a high-fat meal on the oral bioavailability of a single dose of preladenant in healthy subjects.
abstract: The aim of this study was to evaluate the effect of food on the oral bioavailability of preladenant, a novel adenosine A(2A) receptor antagonist. This open-label, randomized, single-dose, 2-way crossover study evaluated the effects of a high-fat, high-calorie meal on the pharmacokinetics of preladenant and its metabolite (SCH434748) following oral administration of a single 25-mg preladenant capsule to 24 healthy subjects. When administered with food, the time of maximum concentration (T(max)) of preladenant was prolonged compared with administration in the fasting state. Whereas T(max) was increased from 0.9 hours to 2.6 hours and maximum concentration (C(max)) was decreased (from 212 ng/mL to 128 ng/mL), the extent of absorption (area under the plasma concentration-time curve from time 0 to time of final quantifiable sample, or AUC([tf])) was unaffected by the meal. Similarly, SCH434748 T(max) was prolonged in the fed state, and C(max) decreased from 43.7 ng/mL to 28.6 ng/mL. The assessment of AUC([tf]) and area under the plasma concentration-time curve from time 0 to infinity [AUC([I])] together suggests that the AUC for the metabolite remained unchanged. No serious, significant, or unexpected adverse events occurred. In summary, food delays absorption and reduces peak exposure (C(max)) but does not alter the extent of preladenant exposure (AUC). These small changes are unlikely to be of clinical importance. A single 25-mg dose of preladenant is safe and well tolerated in healthy subjects under both fed and fasting conditions.
authors.affiliation: Department of Clinical Pharmacology, Merck Sharp & Dohme Corp, PO Box 1000, North Wales, PA 19454, USA. david.cutler@merck.com
authors.forename: David L
authors.initials: DL
authors.lastname: Cutler
authors.forename: Amol
authors.initials: A
authors.lastname: Tendolkar
authors.forename: Igor D
authors.initials: ID
authors.lastname: Grachev
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D059305:Diet, High-Fat; D002149:Energy Intake; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D002214:Capsules; D011743:Pyrimidines; D014230:Triazoles; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine