Mode of administration-dependent pharmacokinetics of bisphosphonates and bioavailability determination

Amnon Hoffman, David Stepensky, Aviva Ezra, Joel M. Van Gelder, Gershon Golomb

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


We investigated the influence of mode of administration on the pharmacokinetics of a clinically used bisphosphonate, pamidronate, and of suberoylbisphosphonate (SuBP), a novel bisacylphosphonate of the P-CO-(C)n-CO-P type, in rats. Serum drug levels and tissue disposition were determined following administration of the drugs by different modes: intravenous bolus (iso-osmotic and hypo-osmotic solutions), continuous intravenous infusion, and peroral administration. Results of the study indicate that the disposition of the bisphosphonates in soft tissue (liver, kidney and spleen) was dependent on route and rate of drug administration, and on the osmoticity of the vehicle. Consequently, main pharmacokinetic parameters (AUC, CL, and Vss) were influenced by the mode of drug administration, precluding accurate determination of bioavailability from AUC values. On the other hand, bone and urine bisphosphonate accumulation were considerably less dependent on mode of administration, and, therefore, are recommended for bioavailability calculation.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - 4 Jun 2001
Externally publishedYes


  • Bioavailability
  • Bisphosphonate
  • Mode of administration dependency
  • Nonlinear pharmacokinetics
  • Pharmacokinetics
  • Volume of distribution

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'Mode of administration-dependent pharmacokinetics of bisphosphonates and bioavailability determination'. Together they form a unique fingerprint.

Cite this