Recombinant human parathyroid hormone 1-34: Pharmacokinetics, tissue distribution and excretion in rats

Zeping Hu, Huisheng Niu, Xiaoxia Yang, Huaifen Li, Guowei Sang, Bo Li

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The objective of this work was to characterize the preclinical pharmacokinetics, tissue distribution, and excretion profiles of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)] in healthy rats. Pharmacokinetic properties of 125I-rhPTH (1-34) were examined after a single subcutaneous (s.c.) and intravenous (i.v.) bolus injection, respectively. Tissue distribution and urinary, fecal, and biliary excretion patterns of 125I-rhPTH (1-34) were also investigated following a single s.c. injection. Our results suggested that rhPTH (1-34) was rapidly distributed and cleared in a bi-exponential manner after a single i.v. bolus injection. Following a single s.c. administration, rhPTH (1-34) exhibited rapid and considerable absorption and declined in a mono-exponential manner, with the absolute bioavailability and elimination half-life of 65% and 3.4-4.1 h, respectively. The TCA-precipitated radioactivity was widely distributed and rapidly diminished in most tissues/organs. Approximately 91% and 2% of the total radioactivity was recovered in urine and feces by 72 h postdosing, respectively; whereas 6% excreted into bile up to 24 h postdosing. These findings indicated high absolute bioavailability, rapid absorption and disposition of rhPTH (1-34) following a single s.c. administration in healthy rats. The accumulation of rhPTH (1-34) in tissues/organs examined appeared to be low. The major elimination route was urinary excretion.

Original languageEnglish (US)
Pages (from-to)144-154
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume317
Issue number2
DOIs
StatePublished - Jul 24 2006

Keywords

  • Bioavailability
  • Distribution
  • Excretion
  • Pharmacokinetics
  • Recombinant human parathyroid hormone (1-34)

ASJC Scopus subject areas

  • Pharmaceutical Science

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