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

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 (V d ) and renal clearance (CL) were consistent across the three single-dose levels for ceftolozane (V d , 15.8-19.5 L; CL, 5.68-6.09 L/h) and tazobactam (V d , 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 center dot mu g/mL; tazobactam, 10.7-48.0 h center dot mu g/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.(c) 2023 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., Rahway, NJ, USA and The Author(s). Published by Elsevier Ltd. on behalf of International Society of Chemotherapy.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study evaluated the pharmacokinetics, safety, and tolerability of C/T in 12 healthy Chinese participants. The results showed that the pharmacokinetics and safety/tolerability of C/T in healthy Chinese participants were comparable to that in other populations, supporting the use of C/T for the treatment of Chinese patients.