Effect of Food on the Bioavailability of Omadacycline in Healthy Participants.

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Tzanis E, Manley A, Villano S, Tanaka SK, Bai S, Loh E

Effect of Food on the Bioavailability of Omadacycline in Healthy Participants.

J Clin Pharmacol. 2017 Mar;57(3):321-327. doi: 10.1002/jcph.814. Epub 2016 Sep 22.

PubMed ID
27539539 [ View in PubMed
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Abstract

Omadacycline is a first-in-class aminomethylcycline antibiotic being evaluated in phase 3 studies as oral and intravenous monotherapy for bacterial infections. This was a phase 1, randomized, open-label, 4-period, crossover study that evaluated the effect of food consumption on the bioavailability of omadacycline. Healthy participant were randomized to 1 of 4 sequences, which included the following predose conditions in different orders (A) >/=6-hour fast, (B) high-fat, nondairy meal 4 hours before dosing, (C) high-fat, nondairy meal 2 hours before dosing, and (D) high-fat meal containing dairy 2 hours before dosing. Participants received a single 300-mg oral dose of omadacycline during each treatment period; periods were separated by >/=5 days. Blood samples for pharmacokinetic (PK) analysis were collected over 24 hours after each dose, and safety assessments were performed during each treatment period. Least-squares mean and 90% confidence intervals were compared for fed state vs fasted state. Thirty-one participants were included in the PK analysis. Fasted AUC0-infinity , AUC0-t , and AUC0-24 were 10.2, 7.2, and 7.2 mug.h/mL, respectively, and Cmax was 0.6 mug/mL. Compared with a fasted dose, bioavailability was reduced by 15% to 17% by a nondairy meal 4 hours before dosing, 40% to 42% by a nondairy meal 2 hours before dosing, and 59% to 63% for a dairy meal 2 hours before dosing. Two participants experienced adverse events (mild nausea, mild somnolence). A 300-mg oral dose of omadacycline administered within 2 to 4 hours after food had reduced bioavailability compared with the fasted state. Oral omadacycline should be administered in a fasted state.

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