Kinetics of isosorbide dinitrate and relationships to pharmacological effects.

Prolonged plasma half‐life after oral isosorbide dinitrate in patients with angina pectoris.

“…The oral clearance of ISDN determined after chronic dosing at 60 mg (Table 1) is significantly slower (P < 0.01) than that previously determined (Fung et al, 1981b) for the same dose after single administration (CLo = 22.1 + 8.9 I/min, mean + s.d. ).…”

“…These patients were admitted to the hospital the day before the study, informed consent was weredrawnatO,0.5, 1.5,2,3,4,5,6,8,10,12, 16,20 and 24 h after dosing. The separated plasma was assayed for ISDN according to a method described previously (Fung et al, 1981b). In two patients, plasma concentrations of the two mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN) were also determined (Morrison & Fung, 1980).…”

“…The presence of this 'hidden' disappearance phase, if confirmed, could provide a partial explanation for the unusual accumulation kinetics of ISDN observed after chronic dosing (Fung et al, 1981b) and for the apparently longer duration of effect of ISDN that could be accounted for by the reportedly short plasma half-life of this and other organic nitrates.…”

“…In a previous study (Fung et al, 1981b) in which we examined the effects of dose and duration of administration of oral isosorbide dinitrate, ISDN, on its pharmacokinetics and pharmacodynamics in chronic angina patients, we had the opportunity to monitor the plasma ISDN concentrations of one patient for 24 h and observed, quite unexpectedly, the existence of an apparent terminal half-life for the unchanged drug of about 4 h. This observation suggests that the plasma disappearance of ISDN in man might not be as fast as had been generally believed, i.e., 0.5 to 1 h (Laufen etal., 1978;Taylor etal., 1980). The presence of this 'hidden' disappearance phase, if confirmed, could provide a partial explanation for the unusual accumulation kinetics of ISDN observed after chronic dosing (Fung et al, 1981b) and for the apparently longer duration of effect of ISDN that could be accounted for by the reportedly short plasma half-life of this and other organic nitrates.…”

Left Ventricular Failure Complicating Acute Myocardial Infarction - Problems and Potential of Nonthrombolytic Therapy

“…For example, the ni trates are often considered to be 'venoselective'. This is true with low doses, but in high doses they also have a dilating effect on the systemic arteriolar resistance vessels [28][29][30]. Phentolamine is frequently considered to be primarily an arteriolar dilator but there is no doubt that it also possesses substantial venodilator activity [31].…”