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- W2002609544 abstract "It has long been believed that organic nitrates, including isosorbide dinitrate (ISDN), are completely metabolized during their first passage through the liver and that oral therapy with this class of compounds is thus irrational. In the past few years, convincing data have been obtained in patients showing that intact ISDN is significantly bioavailable to the systemic circulation after oral administration; the oral bioavailability is about 20% relative to an intravenous dose and about 45% relative to a sublingual dose, with the balance metabolized to isosorbide mononitrates. These pharmacologically active metabolites have longer biologic half-lives than ISDN and are thus believed to contribute to the sustained duration of action of this drug. After acute dosing, changes in the pharmacologic effects of ISDN mirror those in plasma concentration. However, after long-term therapy, partial nitrate tolerance develops despite elevated plasma ISDN concentrations. Available evidence suggests that during sustained dosing, nitrate metabolism is generally reduced throughout the body; thus reduced hepatic and peripheral tissue metabolism raises plasma ISDN concentrations while reduced vascular tissue metabolism decreases the metabolic activation (perhaps to nitrosothiols?) necessary for vascular relaxation." @default.
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- W2002609544 date "1985-07-01" @default.
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- W2002609544 title "Pharmacokinetics and pharmacodynamics of isosorbide dinitrate" @default.
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- W2002609544 doi "https://doi.org/10.1016/0002-8703(85)90489-2" @default.
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