Plasma Disopyramide Concentrations Following a 300-mg Oral Loading Dose in Acute Myocardial Infarction

Weissberg, PL; Matenga, J. A.; Am, Hayler; Holt, D W

doi:10.1097/00007691-198208000-00005

Cited by 7 publications

(4 citation statements)

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“…Our failure to reduce mortality among the patients receiving disopyramide prompts consideration of whether our patients had adequate plasma levels of the drug, particularly in the early phase when mortality is greatest. We based our dosage on the recommendation of Ward and Kinghorn (1976) who had studied the kinetics of disopyramide in AMI and suggested a loading dose of 300 mg, but subsequent reports have cast some doubt on the adequacy of this (Ilett, Madsen and Woods, 1979;Weissberg et aL, 1981).…”

Section: Discussionmentioning

confidence: 99%

Oral disopyramide after admission to hospital with suspected acute myocardial infarction. U. K. Rythmodan Multicentre Study Group

Rythmodan

1984

Postgraduate Medical Journal

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SummaryA multi-centre double-blind randomized study is reported in which the effect on mortality of oral disopyramide (300 mg loading dose, then 100 mg qds) was compared with placebo in 1985 patients entering hospital with suspected acute myocardial infarction. Treatment was commenced with 24 hr of onset of symptoms (mean time to first dose 9 hr) and continued until discharge from hospital or 14 days, whichever came first. Nine-hundred and ninety-five patients were allocated to disopyramide and 990 to placebo. The overall mortality, calculated on an intention-to-treat basis, was 7-2% for the disopyramide and 5-6% for the placebo patients. Among those patients with proven infarction mortality was 9 5% of 687 on disopyramide and 7-4% of 716 on placebo. These differences are not statistically significant. Patients with cardiac failure or hypotension at entry did not fare worse on disopyramide, but those with a conduction defect did. Reinfarction was not significantly influenced by disopyramide. The prophylactic use of disopyramide in patients with suspected acute myocardial infarction does not reduce mortality or the incidence of early reinfarction.

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Section: Discussionmentioning

confidence: 99%

Oral disopyramide after admission to hospital with suspected acute myocardial infarction. U. K. Rythmodan Multicentre Study Group

Rythmodan

1984

Postgraduate Medical Journal

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“…Patients with myocardial infarction achieve lower plasma concentrations of disopyramide after oral administration during the acute phase than during convalescence, presumably due to reduced gastrointestinal absorption (Jounela et al 1982;Kumana et al 1982;Ward & Kinghorn 1976;Weissberg et al 1982). 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.…”

Section: Acute Myocardial Infarctionmentioning

confidence: 99%

Clinical Pharmacokinetics of Disopyramide

Siddoway

Woosley

1986

Clinical Pharmacokinetics

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Disopyramide is an antiarrhythmic agent with proven efficacy in the management of atrial and ventricular arrhythmias. The drug is well absorbed and undergoes virtually no first-pass metabolism. Peak concentrations are achieved approximately 0.5 to 3.0 hours after a dose. Absorption is reduced and slightly slowed in patients with acute myocardial infarction. Disopyramide is excreted as unchanged drug (two-thirds) or as the metabolite mono-N-desisopropyldisopyramide, with elimination via both renal and biliary routes. Elimination half-life is approximately 7 hours in normal subjects and patients, but is prolonged in patients with renal insufficiency (creatinine clearance less than 60 ml/min). Disopyramide exhibits complex protein binding. It is bound to alpha 1-acid glycoprotein (AAG), an acute phase reactant, and binds in a concentration-dependent (saturable) manner. The unbound fraction is reduced in the presence of elevated concentrations of AAG, as are found in acute myocardial infarction and in some chronic haemodialysis patients and renal transplant recipients. Free disopyramide concentrations are low relative to total concentration in these patients. Because the pharmacological effects of disopyramide are determined by unbound drug, changes in the unbound fraction could make total disopyramide concentrations misleading as a guide to therapy. Changes in protein binding do not, however, alter free disopyramide or metabolite concentrations, both of which are dependent only on dosage and intrinsic clearance. Free drug concentration measurement could potentially improve therapeutic monitoring, but is as yet of unproven clinical value. Disopyramide is cleared more rapidly in children than in adults, and therefore children require higher dosages to attain therapeutic concentrations.

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“…In the multiple dose study 10-ml blood specimens were drawn at the following time periods: Day 1: immediately prior to the 6:00 a.m. dose (0 hr) and then at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hr Day 3: 12 hr Day 4: immediately prior to the 6:00 a.m. dose (0 hr) and then at 1, 2, 3, 4, 5, 6,8,10,12,14,16, and 24 hr after the first dose of the day.…”

Section: Collection Of Biological Specimensmentioning

confidence: 99%

“…These findings also indicated less variable absorption of disopyramide from the CR capsules. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) to detect a 20% difference in these AUCss values was 99% at a of 0.05. Using each subject as his own control, the mean bioavailability of disopyramide from the CR capsule was 96.5% of the IR capsule with 95% confidence limits of 88.2 to 104.8%.…”

Section: Multiple Dose Studymentioning

confidence: 99%

Disopyramide Plasma Concentrations Following Single and Multiple Doses of the Immediate- and Controlled-Release Capsules

Karim¹,

Schubert²,

Burns³

et al. 1983

Angiology

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Plasma Disopyramide Concentrations Following a 300-mg Oral Loading Dose in Acute Myocardial Infarction

Cited by 7 publications

References 0 publications

Oral disopyramide after admission to hospital with suspected acute myocardial infarction. U. K. Rythmodan Multicentre Study Group

Oral disopyramide after admission to hospital with suspected acute myocardial infarction. U. K. Rythmodan Multicentre Study Group

Clinical Pharmacokinetics of Disopyramide

Disopyramide Plasma Concentrations Following Single and Multiple Doses of the Immediate- and Controlled-Release Capsules

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