Single- and multiple-dose pharmacokinetics of exendin-4 in rhesus monkeys

International Journal of Pharmaceutics
Guo AiYuanguo Cheng

Abstract

A radioimmunoassay (RIA) for the measurement of exendin-4 concentration in rhesus monkeys serum was developed and validated. The radioimmunoassay described here was sensitive, linear, accurate, precise, and reproducible. Range of the assay was 25-2000 pg/ml. Using this method we characterized the pharmacokinetics and accumulation of exendin-4 in rhesus monkeys. Following s.c. administration at doses rate of 1, 3 and 10 microg/kg, average C(max) ranged from 2.26+/-0.15 to 22.72+/-1.54 ng/ml, and AUC(0-infinity) ranged from 3.43+/-0.05 to 47.1+/-0.10 ng h/ml. As compared to the i.v. administration at a single dose of 3 microg/kg, the absolute bioavailability after s.c. administration were estimated to be 67.3+/-5.3, 75.1+/-4.7 and 72.7+/-8.4% for 1, 3 and 10 microg/kg dose, respectively. After daily s.c. administration at 10 microg/kg for 7 consecutive days, the accumulation ratio was approximately to 1.0, indicating no accumulation upon multiple doses in the monkeys.

Citations

Dec 12, 2012·Pharmaceutical Research·Ting ChenLeonid Kagan
Feb 18, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wei Gao, William J Jusko
Jun 18, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Nicholas T BelloTimothy H Moran
Oct 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vladimir N PodustVolker Schellenberger
Feb 1, 2014·Journal of Veterinary Pharmacology and Therapeutics·C K CebraS J Tornquist
Nov 13, 2018·Basic & Clinical Pharmacology & Toxicology·Michelle Khai Khun Yap, Nurhamimah Misuan
Nov 17, 2009·Nature Biotechnology·Volker SchellenbergerWillem P C Stemmer

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