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 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.
Ai
Guo
G
State Key Laboratory of Pathogen and Biosecurity, Beijing, PR China.
Chen
Zhihang
Z
Shan
Chengqi
C
Che
Jinjing
J
Hou
Yunan
Y
Cheng
Yuanguo
Y
D000818:Animals; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008253:Macaca mulatta; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D011863:Radioimmunoassay; D014688:Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D007457:Iodine Radioisotopes; D010455:Peptides; D014688:Venoms; D000077270:Exenatide