PMID- 35385974
OWN - NLM
STAT- MEDLINE
DCOM- 20220613
LR  - 20220614
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 78
IP  - 7
DP  - 2022 Jul
TI  - Pharmacokinetics of benapenem for injection in subjects with mild to moderate 
      renal impairment.
PG  - 1079-1086
LID - 10.1007/s00228-022-03317-y [doi]
AB  - 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 (AUC(0-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 (AUC(0-inf)_(KBP-3331)/AUC(0-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.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Yang, Haijing
AU  - Yang H
AD  - Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, 
      Shanghai, 200040, China.
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Nephrology, Huashan Hospital, Fudan University, No.12, Middle 
      Wulumuqi Road, Shanghai, 200040, China.
FAU - Chen, Yuancheng
AU  - Chen Y
AD  - Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, 
      Shanghai, 200040, China.
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
FAU - Ren, Hong
AU  - Ren H
AD  - Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Phase I Unit, Shanghai Tongji Hospital, Shanghai, 200065, China.
FAU - Yu, Chen
AU  - Yu C
AD  - Department of Nephrology, Shanghai Tongji Hospital, Shanghai, 200065, China.
FAU - Lu, Jianda
AU  - Lu J
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
AD  - Department of Nephrology, Huashan Hospital, Fudan University, No.12, Middle 
      Wulumuqi Road, Shanghai, 200040, China.
FAU - You, Li
AU  - You L
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
AD  - Department of Nephrology, Huashan Hospital, Fudan University, No.12, Middle 
      Wulumuqi Road, Shanghai, 200040, China.
FAU - Yu, Jicheng
AU  - Yu J
AD  - Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, 
      Shanghai, 200040, China.
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
FAU - Liang, Hong
AU  - Liang H
AD  - Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, 
      Shanghai, 200040, China.
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
FAU - Xiao, Cuilan
AU  - Xiao C
AD  - Xuanzhu Biopharmaceutical Co., Ltd, Beijing, 100025, China.
FAU - He, Zishuang
AU  - He Z
AD  - Xuanzhu Biopharmaceutical Co., Ltd, Beijing, 100025, China.
FAU - Wu, Jufang
AU  - Wu J
AD  - Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, 
      Shanghai, 200040, China.
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China.
FAU - Xue, Jun
AU  - Xue J
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China. xuejun@fudan.edu.cn.
AD  - Department of Nephrology, Huashan Hospital, Fudan University, No.12, Middle 
      Wulumuqi Road, Shanghai, 200040, China. xuejun@fudan.edu.cn.
FAU - Zhang, Jing
AU  - Zhang J
AUID- ORCID: 0000-0003-2966-9149
AD  - Phase I Unit, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, 
      Shanghai, 200040, China. zhangj_fudan@aliyun.com.
AD  - National Clinical Research Center for Geriatric Diseases (Huashan Hospital), 
      Shanghai, 200040, China. zhangj_fudan@aliyun.com.
AD  - China Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and 
      Family Planning Commission, Shanghai, 200040, China. zhangj_fudan@aliyun.com.
LA  - eng
GR  - 2017ZX09304005/Ministry of Science and Technology of the People's Republic of 
      China/
GR  - 03/Shanghai Municipal Human Resources and Social Security Bureau/
PT  - Clinical Trial
PT  - Journal Article
DEP - 20220406
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Carbapenems)
RN  - 0 (benapenem)
SB  - IM
MH  - Area Under Curve
MH  - *Carbapenems/pharmacokinetics
MH  - Humans
MH  - Injections
MH  - *Renal Insufficiency/drug therapy
OTO - NOTNLM
OT  - Benapenem
OT  - Dosing
OT  - Pharmacokinetics
OT  - Renal impairment
OT  - Safety
OT  - Subjects
EDAT- 2022/04/08 06:00
MHDA- 2022/06/14 06:00
CRDT- 2022/04/07 05:03
PHST- 2021/11/30 00:00 [received]
PHST- 2022/03/17 00:00 [accepted]
PHST- 2022/04/08 06:00 [pubmed]
PHST- 2022/06/14 06:00 [medline]
PHST- 2022/04/07 05:03 [entrez]
AID - 10.1007/s00228-022-03317-y [pii]
AID - 10.1007/s00228-022-03317-y [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2022 Jul;78(7):1079-1086. doi: 10.1007/s00228-022-03317-y. 
      Epub 2022 Apr 6.