Pharmacokinetics of nitroglycerin and its dinitrate metabolites over a thirtyfold range of oral doses

Emi Nakashima, Jean F. Rigod, Emil T. Lin, Leslie Z. Benet

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The pharmacokinetics of nitroglycerin and the formation of its dinitrate metabolites (1,2‐glyceryl dinitrate and 1,3‐glyceryl dinitrate) were determined in six healthy volunteers after administration of six oral solution doses ranging from 0.4 mg to 13 mg. ANOVA analysis indicated significant differences between subjects for all Cmax/dose and AUC/dose measurements. No significant difference between doses were noted for these parameters except for AUC/dose for 1,3‐glyceryl dinitrate. The ratio of metabolites (1,2‐metabolite/1,3‐metabolite) for the 0.4 mg dose was significantly different from the ratios for the doses of 1.6 mg or higher. Measurements of the combined residence time parameter suggest nonlinearity in nitroglycerin absorption and metabolism processes of AUMC/AUC between the 0.4 and the 13 mg doses. Consistent results were observed in the AUC ratios of metabolites for 0.4 mg doses of nitroglycerin between oral and sublingual administrations, suggesting that the increased metabolite ratio noted for sublingual nitroglycerin may reflect differences in dose, rather than differences in route of administration. Clinical Pharmacology and Therapeutics (1990) 47, 592–598; doi:

元の言語English
ページ(範囲)592-598
ページ数7
ジャーナルClinical Pharmacology & Therapeutics
47
発行部数5
DOI
出版物ステータスPublished - 1990 5

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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