A single- and multiple-dose study to characterize the pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy Chinese participants.

Na Liu, Xiaohong Wang, Jixiang Zhu, Sumit Basu, Yudong Wei, Bei Yan, Hui Wang, Francheska Colon-Gonzalez, Hwa-Ping Feng, Fang Sun, Haiyan Li, Yanqiao Zang

International journal of antimicrobial agents 2023 Mar

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Ceftolozane/tazobactam (C/T) is approved in several countries to treat complicated urinary tract infections, complicated intra-abdominal infections, and nosocomial pneumonia. There is a paucity of pharmacokinetics and safety data for C/T in Chinese participants. This study evaluated the pharmacokinetics, safety, and tolerability of C/T in 12 healthy Chinese participants after three single administrations of increasing doses (0.75 g, 1.5 g, and 3 g) and multiple administrations of 1.5 g C/T every 8 h for 3 days. After single doses, maximum concentrations of ceftolozane and tazobactam were reached by the end of the 1-h infusion and declined in a biphasic manner thereafter, with mean half-lives of 1.9-2.2 h and 0.74-0.95 h, respectively. Volume of distribution (Vd) and renal clearance (CL) were consistent across the three single-dose levels for ceftolozane (Vd, 15.8-19.5 L; CL, 5.68-6.09 L/h) and tazobactam (Vd, 23.3-28.6 L; CL, 20.8-23.5 L/h). Area under the concentration-time curve (AUC) extrapolated to infinity (ceftolozane, 88.1-328 h∙μg/mL; tazobactam, 10.7-48.0 h∙μg/mL) increased in a dose-dependent manner. After multiple doses over 3 days, AUC from time 0 to 8 h, and concentration at the end of infusion were similar to single-dose measurements (geometric mean ratios, 0.87-1.01 for both drugs). C/T was well tolerated, with no serious adverse events or discontinuations reported; all adverse events were mild. The pharmacokinetics and safety/tolerability of C/T in healthy Chinese participants was comparable to that in previous studies in other populations, supporting the use of C/T for the treatment of Chinese patients. Copyright © 2023. Published by Elsevier Ltd.

Citation

Na Liu, Xiaohong Wang, Jixiang Zhu, Sumit Basu, Yudong Wei, Bei Yan, Hui Wang, Francheska Colon-Gonzalez, Hwa-Ping Feng, Fang Sun, Haiyan Li, Yanqiao Zang. A single- and multiple-dose study to characterize the pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy Chinese participants. International journal of antimicrobial agents. 2023 Mar;61(3):106717