PMID- 31396983
OWN - NLM
STAT- MEDLINE
DCOM- 20200928
LR  - 20210110
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 85
IP  - 12
DP  - 2019 Dec
TI  - Polyethylene glycol loxenatide (PEX168) in subjects with renal impairment: A 
      pharmacokinetic study.
PG  - 2714-2720
LID - 10.1111/bcp.14091 [doi]
AB  - AIMS: 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. METHODS: 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 mug. Pharmacokinetic samples were taken at 0, 24, 48, 72, 
      96, 120, 144, 216, 312, 480, 648 and 720 hours. RESULTS: 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 t(1/2) (163 hours) 
      in the moderate impairment group was prolonged compared to the mild impairment 
      (117 hours) and normal (121 hours) groups. AUC(0-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. CONCLUSION: A single dose of 200 mug 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).
CI  - (c) 2019 The Authors. British Journal of Clinical Pharmacology published by John 
      Wiley & Sons Ltd on behalf of British Pharmacological Society.
FAU - Wang, Jianwen
AU  - Wang J
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Huang, Jie
AU  - Huang J
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Tang, Shiqi
AU  - Tang S
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Sun, Jian
AU  - Sun J
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Zhang, Xianming
AU  - Zhang X
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Liu, Jun
AU  - Liu J
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Yi, Bin
AU  - Yi B
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Liu, Jishi
AU  - Liu J
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
FAU - Zhang, Xingfei
AU  - Zhang X
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Qian
AU  - Yang Q
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Xiaoyan
AU  - Yang X
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Shuang
AU  - Yang S
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
FAU - Yang, Guoping
AU  - Yang G
AUID- ORCID: 0000-0001-5930-586X
AD  - Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South 
      University, Changsha, Hunan, China.
AD  - Research Center of Drug Clinical Evaluation of Central South University, 
      Changsha, Hunan, China.
AD  - Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 
      Hunan, China.
FAU - Zhang, Hao
AU  - Zhang H
AUID- ORCID: 0000-0002-2049-3485
AD  - Department of Nephrology, The Third Xiangya Hospital, Central South University, 
      Changsha, Hunan, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT02467790
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191208
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 0 (polyethylene glycol loxenatide)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Diabetes Mellitus, Type 2/*blood
MH  - Diabetic Nephropathies/*blood
MH  - Dose-Response Relationship, Drug
MH  - Drug-Related Side Effects and Adverse Reactions/etiology
MH  - Female
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/*blood
MH  - Kidney/*metabolism/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Peptides/administration & dosage/adverse effects/*blood
MH  - Polyethylene Glycols/administration & dosage/adverse effects
PMC - PMC6955414
OTO - NOTNLM
OT  - chronic kidney disease
OT  - pharmacokinetics
OT  - phase I trial
OT  - polyethylene glycol loxenatide
OT  - type 2 diabetes mellitus
COIS- There are no competing interests to declare.
EDAT- 2019/08/10 06:00
MHDA- 2020/09/29 06:00
PMCR- 2019/12/08
CRDT- 2019/08/10 06:00
PHST- 2019/01/24 00:00 [received]
PHST- 2019/05/13 00:00 [revised]
PHST- 2019/07/26 00:00 [accepted]
PHST- 2019/08/10 06:00 [pubmed]
PHST- 2020/09/29 06:00 [medline]
PHST- 2019/08/10 06:00 [entrez]
PHST- 2019/12/08 00:00 [pmc-release]
AID - BCP14091 [pii]
AID - 10.1111/bcp.14091 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2019 Dec;85(12):2714-2720. doi: 10.1111/bcp.14091. Epub 2019 
      Dec 8.