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Hepatic extraction of isosorbide dinitrate in cardiac patients
Author(s) -
Morrison R A,
Wiegand UW,
Jähnchen E,
Höhmann D,
Kasper W,
Meinertz T,
Fung HL
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.241
Subject(s) - isosorbide dinitrate , metabolite , first pass effect , active metabolite , medicine , extraction (chemistry) , anesthesia , bioavailability , pharmacokinetics , pharmacology , chemistry , chromatography
Hepatic extraction of organic nitrates, including that of isosorbide dinitrate (ISDN), has been thought to be nearly complete in man but has never been directly measured. We examined the time course of plasma ISDN and metabolite concentrations in arterial and hepatic venous blood in four cardiac patients receiving an intravenous ISDN infusion. Apparent hepatic extraction of ISDN was high (90%) at the beginning of infusion but fell to about 44% 1 hr after termination of infusion. The decrease in ISDN concentration gradient across the liver correlates with an increase in plasma isosorbide‐5‐mononitrate concentration, but a cause‐and‐effect relationship resulting from metabolite inhibition cannot be established. The time‐averaged hepatic extraction of ISDN, at about 70%, agreed with its oral bioavailability in patients. Clinical Pharmacology and Therapeutics (1983) 34 , 724–731; doi: 10.1038/clpt.1983.241