Transdermal bioavailability and first-pass skin metabolism: A preliminary evaluation with nitroglycerin

Emi Nakashima, Patrick K. Noonan, Leslie Z. Benet

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

A model comprising six compartments, a systemic and presystemic compartment for nitroglycerin and each of its two dinitrate metabolites is presented to describe the interrelationships between plasma concentrations of the two metabolites and metabolism in skin after intravenous and transdermal ointment administration of nitroglycerin. Using a perfusion-limited pharmacokinetic model, the equation for the calculation of the fraction (F)of the dose of nitroglycerin systemically available from skin was derived independent of nitroglycerin plasma concentrations. Estimated F values (0.68-0.76) are comparable to values reported in Rhesus monkeys (0.80-0.84). Simulated plasma concentration-time profiles were reasonably fitted to the observed concentrations of nitroglycerin and its two metabolites after transdermal administration. This preliminary model suggests that transdermal bioavailability for a drug metabolized in the skin can be reasonably estimated.

Original languageEnglish
Pages (from-to)423-437
Number of pages15
JournalJournal of Pharmacokinetics and Biopharmaceutics
Volume15
Issue number4
DOIs
Publication statusPublished - 1987 Aug

Keywords

  • nitroglycerin
  • nitroglycerin dinitrate metabolites
  • skin metabolism
  • transdermal bioavailability

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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