Premium
Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.
Author(s) -
Shane SJ,
Iazzetta JJ,
Chisholm AW,
Berka JF,
Leung D
Publication year - 1978
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1978.tb01679.x
Subject(s) - isosorbide dinitrate , pharmacology , oral administration , medicine , oral dose , metabolite , chemistry , anesthesia
1 We have previously reported that vasodilator headache due to isosorbide dinitrate (ISDN) can be circumvented by using small 'priming' doses for an induction period of 1‐2 weeks, after which it is possible to increase to dose rapidly to 360‐720 mg, daily without recurrence of headache and without toxicity. The present study corroborates this earlier finding. 2. Chronic oral administration of doses of ISDN of this order of magnitude results in prolonged high plasma concentrations of the parent compound, as well as higher levels of the metabolites 2‐ISMN and 5‐ISMN. 3. It is our thesis that chronic high oral dosage of ISDN saturates the intrahepatic biotransformation process, and allows high concentrations of ISDN and its metabolites to enter the systemic circulation.