Abstract:

To characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied. Exendin-4 was radioiodinated by the IODOGEN (1,3,4,6-tetrachloro-3 alpha, 6 alphadiphenylglucoluril) method. Pharmacokinetic properties of 125I-exendin-4 were examined after a single s.c. and i.v. injection, respectively. Tissue distribution and urinary, fecal, and biliary excretion patterns of 125I-exendin-4 were also investigated following a single s.c. injection. Exendin-4 was rapidly distributed and cleared with t1/2 of (0.48 ± 0.03) h after a single i.v. injection. Following a single s.c. administration, exendin-4 exhibited rapid and considerable absorption with Tmax of (0.25 ± 0.02) h and declined with the elimination t1/2 of (1.28 ± 0.14) h. The absolute bioavailability was (65.5 ± 10.2) %. The radioactivity was widely distributed and rapidly diminished in most tissues. The kidney contained the highest radioactivity and the distribution of 125I-exendin-4 to the brain was minimal. The major elimination route was urinary excretion. The pharmacokinetic properties of exendin-4 obtained from the present study closely matched those reported in previous studies in rats. Pharmacokinetics profiles of exendin-4 in rats are warranted for the design of future clinical trials.

Key words: Exendin-4, Exendin-4, Iodine, Iodine, Pharmacokinetics, Pharmacokinetics