Merck & Co., Inc., Rahway, New Jersey, USA.
Cognigen Corporation, Simulations Plus Company, Buffalo, New Jersey, USA.
J Clin Pharmacol. 2023 Mar;63(3):352-357. doi: 10.1002/jcph.2165. Epub 2022 Nov 22.
Probability of target attainment (PTA) analyses were conducted to support the recommended ceftolozane/tazobactam dosing regimens, adjusted for renal function, in patients with hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Previously published population pharmacokinetic models describing the disposition of ceftolozane and tazobactam in plasma and epithelial lining fluid (ELF) in patients with HABP/VABP were used to simulate ceftolozane and tazobactam concentration-time profiles in plasma and ELF over the course of 14 days. The simulations were conducted for patients with normal renal function and for patients receiving adjusted doses for mild, moderate, and severe renal impairment. PTA was calculated using established pharmacokinetic/pharmacodynamic targets for ceftolozane and tazobactam. Across renal function groups, plasma PTA was 100% for ceftolozane and >99% for tazobactam; ELF PTA was >99% for ceftolozane and >87% for tazobactam. These results provided support for the currently recommended ceftolozane/tazobactam dosing regimens for HABP/VABP, which were efficacious and well tolerated in the Ceftolozane-Tazobactam Versus Meropenem for Treatment of Nosocomial Pneumonia (ASPECT-NP) trial.
目标达成率（PTA）分析旨在支持推荐的头孢他洛酯/他唑巴坦剂量方案，该方案根据肾功能调整，适用于医院获得性/呼吸机相关性细菌性肺炎（HABP/VABP）患者。先前发表的描述 HABP/VABP 患者体内头孢他洛酯和他唑巴坦在血浆和上皮衬液（ELF）中处置情况的群体药代动力学模型被用于模拟头孢他洛酯和他唑巴坦在血浆和 ELF 中的浓度-时间曲线，持续 14 天。这些模拟针对肾功能正常的患者和接受轻度、中度和重度肾功能损害调整剂量的患者进行。使用头孢他洛酯和他唑巴坦的既定药代动力学/药效学目标计算 PTA。在肾功能各组中，头孢他洛酯的血浆 PTA 为 100%，他唑巴坦的 PTA >99%；头孢他洛酯的 ELF PTA >99%，他唑巴坦的 PTA >87%。这些结果为目前推荐的用于 HABP/VABP 的头孢他洛酯/他唑巴坦剂量方案提供了支持，该方案在头孢他洛酯-他唑巴坦与美罗培南治疗医院获得性肺炎（ASPECT-NP）试验中具有疗效且耐受性良好。
