Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 95, Issue 11, Pages 2499-2506Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/jps.20720
Keywords
hPTH (1-34); hepatic extraction; intraportal vein administration; peptide delivery; pharmacokinetics; saturation
Ask authors/readers for more resources
The pharmacokinetics (PK) and hepatic extraction (E-H) of human PTH (1-34), hPTH (1-34), were characterized in rat, dog, and monkey, following intraportal (IPO) and intravenous (IV) bolus administration. hPTH (1-34) was administered to Sprague-Dawley rats (2, 10, 100 mu g/kg), beagle dogs (3, 6 mu g/kg), and rhesus monkeys (6, 30 mu g/kg). Serum concentrations of immunoreactive hPTH (1-34) were used to derive PK parameters. IPO bioavailability (F-IPO) was determined by comparing dose-normalized serum exposure (i.e., AUC(IPO)/AUC(IV)). E-H was estimated as 1-F-IPO. In all species, greater than dose-proportional increases in exposure (i.e., C-max and AUC) were observed for both routes. Dose-dependent disposition (i.e., time-average clearance (CL) and half-life (t(1/2)) were observed in all three species. In rats, E-H values of 71% (2 mu g/kg), 35% (10 mu g/kg), and < 1% (100 mu g/kg) were obtained. In dogs, E-H values of 90% (3 mu g/kg) and 66% (6 mu g/kg) were obtained. In monkeys, E-H values of 25% (6 mu g/kg) and < 1% (30 mu g/kg) were observed. In conclusion, hPTH (1-34) is subject to hepatic first pass extraction in rat, dog, and monkey with evidence of saturation in the rat. Saturable hepatic extraction in dog and monkey is inconclusive due to the limited dose range investigated. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available