The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathyroid hormone [rhPTH （1-34）] in Rhesus monkeys after single and multiple subcutaneous administration. An immunoradiometric assay （IRMA） was used to determine the plasma drug concentration of rhFFH （1-34） after giving single dose of 10, 20 and 40 ug/kg and daily dose of 40 ug/kg for 7 d by subcutaneous administration, and intravenous injection of 20 ug/kg in Rhesus monkeys. The pharmacokinetic parameters were calculated by noncompartmental analysis. The drug plasma level quantitation range was from 0.027 to 2.22 ng/mL. The intra- and inter-assay precision （CV） of analysis were less than 15%, and the average recovery was about 93.0% ± 8.6% - 116.5% ± 14.0%. After subcutaneous administration of rhPTH（1-34） at dose of 10, 20 and 40 ug/kg, the average Tmax was 0.67, 0.5 and 0.83 h, Cmax were 1.85 ± 0.05, 3.23 ± 0.25 and 7.15 ± 1.19 ng/mL, the AUC（0-∞） were 3.4 ± 0.6, 10.7 ± 1.3 and 12.6 ± 1.5 ng/h/mL, and terminal-phase elimination T1/2 were 0.72 ± 0.10, 1.15 ± 0.10 and 1.03 ± 0.06 h, respectively. The absolute bioavailability of rhPTH （1-34） was 46.96% after subcutaneous administration of 20 ug/kg. There was no evidence of accumulation during systemic exposure of rhPTH （1-34） upon multiple dosing in Rhesus monkeys. The IRMA assay method provide reasonable sensitivity and specificity for the pharrnacokinetic study of rhPTH （1-34） after subcutaneous or intravenous administration in Rhesus monkeys. The pharmacokinetic characteristic of rhPTH （1-34） in monkeys shows linear relationship with the dose administered subcutaneously.
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. Pharrnacokinetic properties of ^125I-exendin-4 were examined after a single s.c. and i.v. injection, respectively. Tissue distri- bution 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.
