Pharmacokinetic and pharmacodynamic evaluation of intermittent versus continuous alendronate administration in rats

David Stepensky, Gershon Golomb, Amnon Hoffman

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


We studied the differences in phormacokinetics and pharmacodynamics of the same dose of alendronate administered subcutaneously as intermittent bolus injection or continuous infusion in rats. Two rat models of bone disease were applied. Bone cancer was produced by intratibial inoculation of Walker carcinosarcoma cells, and a model of augmented bone resorption was produced by vitamin D3 treatment of rats that had undergone thyroidparathyroidectomy. Higher amounts of alendronate were found in bones and in internal organs after bolus drug administration as compared with continuous infusion. Drug effects on plasma calcium levels and on urine calcium excretion were similar in both modes of alendronate administration. Results of the study indicate that the pharmacokinetics (disposition) of alendronate is administration-dependent. The total amount found in bone does not directly represent the amount of alendronate that is pharmacologically active at the site of action in the bone and that affects bone remodeling. The findings suggest that there is no pharmacodynamic advantage for continuous infusion of alendronate. It is concluded that the preferred mode of administration should be selected according to secondary clinical criteria (like incidence of adverse effects and convenience of administration).

Original languageEnglish
Pages (from-to)508-516
Number of pages9
JournalJournal of Pharmaceutical Sciences
Issue number2
StatePublished - 1 Jan 2002
Externally publishedYes


  • Alendronate
  • Bisphosphonates
  • Mode of administration dependency
  • Pharmacodynamics
  • Pharmocokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science


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