title: Effect of a high-calorie, high-fat meal on the bioavailability and pharmacokinetics of PA-824 in healthy adult subjects.
abstract: PA-824 is a novel nitroimidazo-oxazine being developed as an antituberculosis agent. Two randomized studies evaluated the pharmacokinetics and safety of a single oral dose of PA-824 administered to healthy adult subjects 30 min after a high-calorie, high-fat meal (fed state) versus after a minimum 10-h fast (fasted state). A total of 48 subjects were dosed in the two studies in a randomized crossover design with PA-824 at dose levels of 50, 200, or 1,000 mg in the fed state or fasted state. After the administration of PA-824, the geometric mean ratios of Cmax and AUC0-∞ revealed an increase in exposure with the addition of a high-calorie, high-fat meal compared to the fasted state by 140 and 145% at 50 mg, 176 and 188% at 200 mg, and 450 and 473% at 50, 200, and 1,000 mg, respectively. The median Tmax in the fed state was 4 h for the 50-mg dose and 5 h for the 200- and 1,000-mg doses. In the fasted state, the median Tmax was 4 h for the 50- and 200-mg doses and 6.5 h for the 1,000-mg dose. All doses were well tolerated, and no serious adverse events occurred in either study. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01828827 and NCT01830439.).
authors: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors: Helen
authors: H
authors: Winter
authors: Ann
authors: A
authors: Ginsberg
authors: Erica
authors: E
authors: Egizi
authors: Ngozi
authors: N
authors: Erondu
authors: Karl
authors: K
authors: Whitney
authors: Elliott
authors: E
authors: Pauli
authors: Daniel
authors: D
authors: Everitt
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000995:Antitubercular Agents; D004041:Dietary Fats; D009593:Nitroimidazoles; C410767:pretomanid
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