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

  • Emi Nakashima
  • Patrick K. Noonan
  • Leslie Z. Benet
Article

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 Fvalues (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.

Key words

nitroglycerin nitroglycerin dinitrate metabolites transdermal bioavailability skin metabolism 

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Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • Emi Nakashima
    • 1
  • Patrick K. Noonan
    • 1
  • Leslie Z. Benet
    • 1
  1. 1.Department of Pharmacy, School of PharmacyUniversity of CaliforniaSan Francisco

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