Pharmacokinetics of Teriparatide (rhPTH[1-34]) and Calcium Pharmacodynamics in Postmenopausal Women With Osteoporosis

Calcif Tissue Int. 2010 Dec;87(6):485-92. doi: 10.1007/s00223-010-9424-6. Epub 2010 Oct 16.

Abstract

Teriparatide (rhPTH[1-34]) affects calcium metabolism in a pattern consistent with the known actions of endogenous parathyroid hormone (PTH). This report describes the pharmacokinetics and resulting serum calcium response to teriparatide in postmenopausal women with osteoporosis. Pharmacokinetic samples for this analysis were obtained from 360 women who participated in the Fracture Prevention Trial. Postmenopausal women with osteoporosis received daily subcutaneous injections of either teriparatide 20 μg (4.86 μmol) or placebo, median 21 months' treatment. Serum teriparatide and calcium concentrations were measured throughout the study. An indirect-response model was developed to describe the pharmacokinetic-pharmacodynamic relationship between teriparatide concentrations and serum calcium response. The pharmacokinetics of teriparatide were characterized by rapid absorption (maximum concentration achieved within 30 min) and rapid elimination (half-life of 1 h), resulting in a total duration of exposure to the peptide of approximately 4 h. Teriparatide transiently increased serum calcium, with the maximum effect observed at approximately 4.25 h (median increase 0.4 mg/dl [0.1 mmol/l]). Calcium concentrations returned to predose levels by 16-24 h after each dose. Persistent hypercalcemia was not observed; one teriparatide 20 μg-treated patient had a predose serum calcium value above the normal range but <11.0 mg/dl (2.75 mmol/l). Following once-daily subcutaneous administration, teriparatide produces a modest but transient increase in serum calcium, consistent with the known effects of endogenous PTH on mineral metabolism. The excursion in serum calcium is brief, due to the short length of time that teriparatide concentrations are elevated.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / blood
  • Bone Density Conservation Agents / pharmacokinetics*
  • Bone Density Conservation Agents / therapeutic use
  • Calcium / blood*
  • Female
  • Fractures, Bone / drug therapy
  • Humans
  • Hypercalcemia / drug therapy
  • Middle Aged
  • Osteoporosis, Postmenopausal / blood*
  • Osteoporosis, Postmenopausal / drug therapy
  • Teriparatide / blood
  • Teriparatide / pharmacokinetics*
  • Teriparatide / therapeutic use

Substances

  • Bone Density Conservation Agents
  • Teriparatide
  • Calcium