Pharmacokinetics and Pharmacodynamics of Oral and Intravenous Omadacycline.

ABSTRACT: Oral and intravenous (IV) omadacycline formulations are approved in the United States for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adults. Oral omadacycline bioavailability is 34.5%; similar exposures are obtained following 300 mg oral and 100 mg IV doses. Oral administration should be in a fasted state, with dairy products, antacids, or multivitamins avoided for ?4 hours after dosing. Low protein binding (21%), large volume of distribution (190 L), low systemic clearance (10 L/hour), and long elimination half-life (16-17 hours) support once-daily dosing. Omadacycline is excreted unchanged in feces (81.1%) and urine (14.4%), with low potential for drug-drug interactions. Dose adjustments are unnecessary for age, sex, and renal or hepatic impairment. Pharmacokinetic-pharmacodynamic studies identify fAUC0-24/MIC ratio as the parameter that correlates with in vivo efficacy. Systemic exposure of omadacycline in epithelial lining fluid is greater than/equal to plasma concentrations in healthy adults.

SUBMITTER: Rodvold KA 

PROVIDER: S-EPMC6669312 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature