Abstract
Objective
This study evaluated the pharmacokinetic (PK) characteristics of benapenem in subjects with mild to moderate renal impairment to provide a reference for benapenem dosing regimens in this patient population.
Methods
Eighteen subjects were enrolled in this study. Each subject received a single dose of benapenem intravenously (1.0 g in 100 ml of 0.9% saline) followed by blood and urine collection to measure the concentrations of benapenem and its major metabolite. PK analysis was performed to evaluate the effect of varying degrees of renal impairment on the PK characteristics of benapenem. The safety of benapenem was also evaluated.
Results
In subjects with normal renal function, mild renal impairment, and moderate renal impairment, the maximum plasma benapenem concentrations were 163 ± 6.58 mg/L, 138 ± 17.4 mg/L, and 134 ± 0.11 mg/L, respectively (15.3% and 17.8% lower in subjects with mild and moderate renal impairment, respectively, than in subjects with normal renal function). The areas under the plasma concentration–time curve (AUC0-inf) were 1153.67 ± 143.2 mg·h/L, 1129.17 ± 241.41 mg·h/L, and 1316.46 ± 229.83 mg·h/L, respectively (P > 0.05); the cumulative urinary excretion rates at 72 h after dosing were 52.61 ± 8.58%, 39.42 ± 8.35%, and 29.84 ± 9.15%, respectively; and the metabolic ratio (AUC0-inf_KBP-3331/AUC0-inf_benapenem) were 3.96 ± 0.35%, 5.56 ± 0.82%, and 8.24 ± 0.85%, respectively. No drug-related adverse events (AEs), serious AEs, or AEs leading to withdrawal occurred in this study.
Conclusion
No adjustment to benapenem dosing is needed in patients with mild to moderate renal impairment.
Clinical trial registration
Drug clinical trial registration and information publicity platform: http://www.chinadrugtrials.org.cn/index.html. Registration number: CTR20190760.
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Data availability
The data in this article belong to the sponsor. The data may be made available to readers with permission from the corresponding author and sponsor.
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Acknowledgements
We sincerely thank the researchers at the Phase I Unit and Department of Nephrology, Huashan Hospital, Fudan University, the Phase I Unit and Department of Nephrology, Shanghai Tongji Hospital, and the Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine for their contributions to this study.
Funding
This work was supported by a grant from Shanghai municipal Human Resources and Social Security Bureau (no. 03) and the New Drug Creation and Manufacturing Program of the Ministry of Science and Technology of China (no. 2017ZX09304005). The clinical trial was sponsored by Xuanzhu Co., Ltd.
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HY and MZ coordinated the clinical trial and wrote the manuscript. JZ, JX, HR, HZ, and CY designed and performed the research. CX and ZH participated in the design of the research. YC participated in the analysis and interpretation of the data. JL, LY, JY, HL and JW performed the clinical trial.
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CX is a full-time employee of Xuanzhu Biopharmaceutical Co., Ltd. ZH was the employee of Xuanzhu Co., Ltd when the study was ongoing. Other authors declare no competing interests.
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Yang, H., Zhang, M., Chen, Y. et al. Pharmacokinetics of benapenem for injection in subjects with mild to moderate renal impairment. Eur J Clin Pharmacol 78, 1079–1086 (2022). https://doi.org/10.1007/s00228-022-03317-y
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DOI: https://doi.org/10.1007/s00228-022-03317-y