Pulmonary Associates, Phoenix, Arizona, USA.
College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.01135-17. Print 2017 Sep.
The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h 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 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC values were 17.23 mg · h/liter and 1.47, respectively. The AUC value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.
在 58 名健康成年受试者中获得了 omadacycline 和 tigecycline 在血浆、上皮衬液（ELF）和肺泡细胞（AC）中的稳态浓度。受试者分别给予 omadacycline 100mg 静脉注射（i.v.），每 12 小时一次，共 2 剂，然后每 24 小时一次，共 3 剂；或给予 tigecycline 初始剂量 100mg i.v.，然后每 12 小时一次，共 6 剂 50mg i.v.。在 omadacycline 第五剂开始后 0.5、1、2、4、8、12 或 24 小时和 tigecycline 第七剂开始后 2、4、6 或 12 小时，对每位受试者进行支气管镜检查和支气管肺泡灌洗。基于平均浓度，ELF 和 AUC 值中基于 AUC 值的 ELF 与总血浆 omadacycline 浓度之比的时间零至 24 小时后给药（AUC）（基于 AUC 值）的 AUC 值分别为 17.23mg·h/L 和 1.47。AC 的 AUC 值为 302.46mg·h/L，AC 与总血浆 omadacycline 浓度之比为 25.8。相比之下，基于 tigecycline 在 ELF 和 AC 中的 AUC 值的平均浓度，AUC 值在时间零至 12 小时后给药（AUC）分别为 3.16 和 38.50mg·h/L。基于 AUC 值，ELF 和 AC 与总血浆 tigecycline 浓度之比分别为 1.71 和 20.8。与 tigecycline 相比，omadacycline 在血浆、ELF 和 AC 中的浓度更高且更持久，其药代动力学优势表明 omadacycline 是一种有前途的治疗敏感病原体引起的下呼吸道细菌感染的抗菌药物。
