Pharmacokinetics in rats of a long-acting human parathyroid hormone-collagen binding domain peptide construct

Robert Stratford, Christopher Vu, Joshua Sakon, Ranjitha Katikaneni, Robert Gensure, Tulasi Ponnapakkam

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)768-775
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Collagen binding
  • Osteoporosis
  • PTH(1-34)
  • Peptide delivery
  • Peptides
  • Pharmacokinetic/pharmacodynamic models
  • Population pharmacokinetics
  • Preclinical pharmacokinetics
  • Teriparatide

ASJC Scopus subject areas

  • Pharmaceutical Science

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