Disopyramide pharmacokinetics during recovery from myocardial infarction.

Abstract

1 Previous pharmacokinetic studies of disopyramide in patients with ischaemic heart disease include unexplained reports of poor bioavailability and extremely long elimination half-lives which undermine accepted dosage recommendations. 2 Disopyramide pharmacokinetics were investigated after intravenous and oral administration to nine such patients. 3 Mean elimination half-life (6.82 h) and bioavailability (79.8%) were consistent with findings from a previous study in young healthy volunteers. 4 Volume of distribution was reduced by 25%: the mean ± s.d. value was 0.61 ± 0.17 1/kg. Total body clearance was significantly reduced: the mean + s.d. value was 1.02 + 0.16 ml min-' kg-'. 5 These figures indicate that, in this patient group, if renal function is not significantly impaired, a standard loading dose of 2 mg/kg should be followed by the appropriate maintenance dose administered three or four times daily.

Sustained release disopyramide compared to plain capsules after change‐ over from intravenous infusion.

“…In the unstable acute phase of myocardial infarction the renal function may fluctuate, and the pharmacokinetics of disopyramide are probably also otherwise affected (Bryson et al, 1982;Ilett et al, 1979;Landmark et al, 1981). Changes in binding to acute phase proteins of a basic drug like disopyramide (Piafsky et al, 1975;Lima et al, 1981) is a possible source of error in the interpretation of the total concentration and the pharmacokinetic data.…”

“…Unfortunately, calculation of the dose is complicated by the altered disposition of disopyramide in myocardial infarction and heart failure (Bryson et al, 1982;Ilett et al, 1979;Landmark et al, 1981). In the acutely ill patient who often has delayed gastric emptying due to nausea or the effect of strong analgesics (Nimmo, 1976), oral medication may be unreliable (Kumana etal., 1982;Weissberg etal., 1982).…”

“…In the acutely ill patient who often has delayed gastric emptying due to nausea or the effect of strong analgesics (Nimmo, 1976), oral medication may be unreliable (Kumana etal., 1982;Weissberg etal., 1982). 71 In order to avoid excessive variation of the plasma concentration plain disopyramide tablets or capsules are administered 6-or 8-hourly (Heel et al, 1978;Bryson et al, 1982). We were interested to examine whether sustained release (SR) tablets given at 12 h intervals could be safely used in the acute phase of myocardial infarction complicated by arrhythmias.…”

Clinical Pharmacokinetics of Disopyramide

“…This reduction of absorption is more severe in myocardial infarction complicated by congestive heart failure and also may be worsened by administration of narcotic analgesics or antiemetics. Renal clearance, tmax, and elimination half-life of disopyramide are not altered during myocardial infarction (Bryson et al 1982a;Hett et al 1979;Johnston et al 1980;Jounela et al 1982).…”

“…Elimination half-life in normal subjects is 4.4 to 7.8 hours (Bryson et al 1978;Karim 1975). In patients with acute myocardial infarction, unstable an~na pectoris, or symptomatic arrhythmias and with normal renal function, elimination half-life is more variable, ranging from 6 to 15 hours (Bryson et al 1982a;Jounela et al 1982;Landmark et al 1981;Rangno et al 1976;Ward & Kinghorn 1976).…”