Pharmacokinetics in Rats of a Long-Acting Human Parathyroid Hormone-Collagen Binding Domain Peptide Construct
by Stratford, Jr, Robert; Vu, Christopher; Sakon, Josh; Katikaneni, Ranjitha; Gensure, Robert C.; Ponnapakkam, Tulasi
The pharmacokinetics of a hybrid peptide consisting of the N-terminal biol. active region of human parathyroid hormone (PTH) linked to a collagen-binding domain (CBD) were evaluated in female Sprague-Dawley rats. The peptide, PTH-CBD, consists of the first 33 amino acids of PTH linked as an extension of the amino acid chain to the CBD peptide derived from ColH collagenase of Clostridium histolyticum. Serum concns. arising from single dose administration by the s.c. and i.v. routes were compared with those measured following route-specific mole equiv. doses of PTH(1-34). Population-based modeling demonstrated similar systemic absorption kinetics and bioavailability for both peptides. Exposure to PTH-CBD was sixfold higher because of a systemic clearance of approx. 20% relative to PTH(1-34); however, these kinetics were consistent with more than 95% of a dose being eliminated from serum within 24 h. Results obtained support continued investigation of PTH-CBD as a bone-targeted anabolic agent for the treatment of postmenopausal osteoporosis. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Assocn. J Pharm Sci.
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- 1520-6017; 0022-3549