title: Clinical disposition, metabolism and in vitro drug-drug interaction properties of omadacycline.
abstract: 1. Absorption, distribution, metabolism, transport and elimination properties of omadacycline, an aminomethylcycline antibiotic, were investigated in vitro and in a study in healthy male subjects. 2. Omadacycline was metabolically stable in human liver microsomes and hepatocytes and did not inhibit or induce any of the nine cytochrome P450 or five transporters tested. Omadacycline was a substrate of P-glycoprotein, but not of the other transporters. 3. Omadacycline metabolic stability was confirmed in six healthy male subjects who received a single 300 mg oral dose of [14C]-omadacycline (36.6 μCi). Absorption was rapid with peak radioactivity (∼610 ngEq/mL) between 1-4 h in plasma or blood. The AUClastof plasma radioactivity (only quantifiable to 8 h due to low radioactivity) was 3096 ngEq h/mL and apparent terminal half-life was 11.1 h. Unchanged omadacycline reached peak plasma concentrations (∼563 ng/mL) between 1-4 h. Apparent plasma half-life was 17.6 h with biphasic elimination. Plasma exposure (AUCinf) averaged 9418 ng h/mL, with high clearance (CL/F, 32.8 L/h) and volume of distribution (Vz/F 828 L). No plasma metabolites were observed. 4. Radioactivity recovery of the administered dose in excreta was complete (>95%); renal and fecal elimination were 14.4% and 81.1%, respectively. No metabolites were observed in urine or feces, only the omadacycline C4-epimer.
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Jimmy
authors: J
authors: Flarakos
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Yancy
authors: Y
authors: Du
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Helen
authors: H
authors: Gu
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Lai
authors: L
authors: Wang
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Heidi J
authors: HJ
authors: Einolf
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Dung Y
authors: DY
authors: Chun
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Bing
authors: B
authors: Zhu
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Natalia
authors: N
authors: Alexander
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Adrienne
authors: A
authors: Natrillo
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Imad
authors: I
authors: Hanna
authors: d Clinical Pharmacology, Gilead Sciences , Foster City , CA , USA.
authors: Lillian
authors: L
authors: Ting
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Wei
authors: W
authors: Zhou
authors: b Translational Medicine, Novartis Institutes for Biomedical Research, DMPK , East Hanover , NJ , USA.
authors: Kiran
authors: K
authors: Dole
authors: a Drug Metabolism and Pharmacokinetics and.
authors: Haiying
authors: H
authors: Sun
authors: b Translational Medicine, Novartis Institutes for Biomedical Research, DMPK , East Hanover , NJ , USA.
authors: Steven J
authors: SJ
authors: Kovacs
authors: b Translational Medicine, Novartis Institutes for Biomedical Research, DMPK , East Hanover , NJ , USA.
authors: Daniel S
authors: DS
authors: Stein
authors: c Paratek Pharmaceuticals, Clinical and Medical Affairs , King of Prussia , PA , USA , and.
authors: S Ken
authors: SK
authors: Tanaka
authors: c Paratek Pharmaceuticals, Clinical and Medical Affairs , King of Prussia , PA , USA , and.
authors: Stephen
authors: S
authors: Villano
authors: a Drug Metabolism and Pharmacokinetics and.
authors: James B
authors: JB
authors: Mangold
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D019540:Area Under Curve; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D013754:Tetracyclines / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000900:Anti-Bacterial Agents; D013754:Tetracyclines; C000591640:omadacycline; D003577:Cytochrome P-450 Enzyme System
keywords: Aminomethylcycline; cytochrome P450; human; transporters