2. Academic Validation
  3. Pharmacokinetics of benapenem for injection in subjects with mild to moderate renal impairment

Pharmacokinetics of benapenem for injection in subjects with mild to moderate renal impairment

  • Eur J Clin Pharmacol. 2022 Jul;78(7):1079-1086. doi: 10.1007/s00228-022-03317-y.
Haijing Yang 1 2,  Min Zhang 3,  Yuancheng Chen 1 2,  Hong Ren 4,  Hong Zhang 5,  Chen Yu 6,  Jianda Lu 2 3,  Li You 2 3,  Jicheng Yu 1 2,  Hong Liang 1 2,  Cuilan Xiao 7,  Zishuang He 7,  Jufang Wu 1 2,  Jun Xue 8 9,  Jing Zhang 10 11 12
Affiliations

Affiliations

  • 1 Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China.
  • 2 National Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, 200040, China.
  • 3 Department of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China.
  • 4 Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
  • 5 Phase I Unit, Shanghai Tongji Hospital, Shanghai, 200065, China.
  • 6 Department of Nephrology, Shanghai Tongji Hospital, Shanghai, 200065, China.
  • 7 Xuanzhu Biopharmaceutical Co., Ltd, Beijing, 100025, China.
  • 8 National Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, 200040, China. xuejun@fudan.edu.cn.
  • 9 Department of Nephrology, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China. xuejun@fudan.edu.cn.
  • 10 Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China. zhangj_fudan@aliyun.com.
  • 11 National Clinical Research Center for Geriatric Diseases (Huashan Hospital), Shanghai, 200040, China. zhangj_fudan@aliyun.com.
  • 12 China Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, 200040, China. zhangj_fudan@aliyun.com.
PMID: 35385974 DOI: 10.1007/s00228-022-03317-y
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.

Keywords

Benapenem; Dosing; Pharmacokinetics; Renal impairment; Safety; Subjects.

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