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Polyethylene glycol loxenatide (PEX168) in subjects with renal impairment: A pharmacokinetic study.

Authors
  • Wang, Jianwen1
  • Huang, Jie2
  • Li, Wei1
  • Tang, Shiqi1
  • Sun, Jian1
  • Zhang, Xianming1
  • Liu, Jun1
  • Yi, Bin1
  • Liu, Jishi1
  • Zhang, Xingfei2
  • Yang, Qian2
  • Yang, Xiaoyan2
  • Yang, Shuang2
  • Yang, Guoping2, 3, 4
  • Zhang, Hao1
  • 1 Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. , (China)
  • 2 Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. , (China)
  • 3 Research Center of Drug Clinical Evaluation of Central South University, Changsha, Hunan, China. , (China)
  • 4 Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China. , (China)
Type
Published Article
Journal
British Journal of Clinical Pharmacology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Dec 01, 2019
Volume
85
Issue
12
Pages
2714–2720
Identifiers
DOI: 10.1111/bcp.14091
PMID: 31396983
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Type 2 diabetes mellitus (T2DM) is commonly complicated by renal impairment. Polyethylene glycol loxenatide (PEX168) is a novel long-acting glucagon-like peptide-1 receptor agonist for T2DM. PEX168 pharmacokinetics was studied to identify requirements for dose-modification in T2DM complicated by renal impairment. This was a single-centre, open-labelled, parallel-group, single-dose, phase I clinical trial of patients with mild and moderate renal impairment, and with or without T2DM. Age-, sex- and body mass index-matched subjects with normal renal function, and with or without T2DM were recruited as controls. Subjects received a single abdominal subcutaneous injection of PEX168 200 μg. Pharmacokinetic samples were taken at 0, 24, 48, 72, 96, 120, 144, 216, 312, 480, 648 and 720 hours. Twenty-three patients were included in the pharmacokinetics analysis. Vz/F and CL/F were lower in the moderate impairment group than in the other groups. The mean t1/2 (163 hours) in the moderate impairment group was prolonged compared to the mild impairment (117 hours) and normal (121 hours) groups. AUC0-inf increased by 13 and 100.7% in patients with mild and moderate renal impairment, respectively. Most adverse events were mild gastrointestinal disorders, with only 1 serious adverse event observed. A single dose of 200 μg of PEX168 was in general well tolerated in patients with renal impairment. The in vivo clearance rate of PEX168 in patients with moderate renal impairment is slower than in patients with mild renal impairment and normal renal function and dose adjustment might be required (ClinicalTrials.org #NCT02467790). © 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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