Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells in Healthy Adult Subjects [PublishAheadOfPrint]

The steady-state concentrations of omadacycline and tigecycline in plasma, epithelial lining fluid (ELF), and alveolar cells (AC) concentrations were obtained in 58 healthy adult subjects. Subjects were administered either omadacycline as 100 mg intravenously (IV) every 12 hours for two doses followed by 100 mg IV every 24 hours for three doses or tigecycline as an initial dose of 100 mg IV followed by 50 mg IV every 12 hours for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 hours, and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 hours. The AUC_0-24 value (based on mean concentrations) in ELF and the ratio of ELF to total plasma omadacycline based on AUC_0-24 values were 17.23 mg·h/L and 1.47, respectively. The AUC_0-24 value in AC was 302.46 mg·h/L and the ratio of AC to total plasma omadacycline concentrations was 25.8. In comparison, AUC_0-12 values based on mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg·h/L, respectively. The ratio of ELF and AC to total plasma concentrations of tigecycline based on AUC_0-12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline in plasma, ELF, and AC compared to tigecycline suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.

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