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

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 μg/kg, average Cmax ranged from 2.26 ± 0.15 to 22.72 ± 1.54 ng/ml, and AUC0–∞ 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 μg/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 μg/kg dose, respectively. After daily s.c. administration at 10 μg/kg for 7 consecutive days, the accumulation ratio was approximately to 1.0, indicating no accumulation upon multiple doses in the monkeys.