title: Pharmacokinetics in rats of a long-acting human parathyroid hormone-collagen binding domain peptide construct.
abstract: The pharmacokinetics of a hybrid peptide consisting of the N-terminal biologically 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 concentrations arising from single dose administration by the subcutaneous and intravenous routes were compared with those measured following route-specific mole equivalent 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 approximately 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.
authors.affiliation: College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana, 70130.
authors.forename: Robert
authors.initials: R
authors.lastname: Stratford
authors.forename: Christopher
authors.initials: C
authors.lastname: Vu
authors.forename: Joshua
authors.initials: J
authors.lastname: Sakon
authors.forename: Ranjitha
authors.initials: R
authors.lastname: Katikaneni
authors.forename: Robert
authors.initials: R
authors.lastname: Gensure
authors.forename: Tulasi
authors.initials: T
authors.lastname: Ponnapakkam
mesh_terms: D000818:Animals; D001682:Biological Availability; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D003012:Microbial Collagenase / Q000737:chemistry; D015233:Models, Statistical; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C546964:CCBE1 protein, human; D002135:Calcium-Binding Proteins; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010455:Peptides; D025521:Tumor Suppressor Proteins; D003012:Microbial Collagenase
keywords: PTH(1-34); collagen binding; osteoporosis; peptide delivery; peptides; pharmacokinetic/pharmacodynamic models; population pharmacokinetics; preclinical pharmacokinetics; teriparatide