Plasma levels of disopyramide after administration of conventional capsules and sustained-release tablets. 1983

I L Nauta, and J van de Calseyde, and D P Hertzberger

A study was carried out in 33 patients with myocardial infarction and complicating arrhythmias to compare plasma levels of disopyramide attained after administration of conventional capsules or sustained-release tablets. On Day 1, 29 patients started treatment wtih 600 mg disopyramide in 3 divided doses of conventional capsules. In 18, disopyramide plasma concentrations of 3 mg/l or more were achieved within 300 minutes after the first dose. On the second day, patients were allocated at random to receive treatment double-blind for 11 days with 500 mg disopyramide daily given either as conventional capsules (17 patients) or as sustained-release tablets (16 patients). Plasma concentrations were measured just before and 3 hours after the morning dose. Mean maximum and minimum concentrations in the conventional capsule group were 4.4 mg/l and 2.8 mg/l, respectively, compared to 4.3 mg/l and 3.0 mg/l, respectively, in the sustained-release tablet group. For the next 30 days all patients continued treatment with sustained-release tablets. Mean disopyramide plasma concentration measured 15 to 18 hours after the last dose was 2.8 mg/l. Myocardial function was estimated during and 1 week after discontinuing disopyramide treatment. The mean fractional fibre shortening (echocardiography) during treatment was 23% less than that 1 week after discontinuation. The mean PEP/LVET (systolic time interval recording) was 7% higher during treatment compared with 1 week after discontinuation. In 4 cases, mean ejection fraction, measured by scintigraphic methods, during treatment was 10% less than 1 week after discontinuation. Anti-arrhythmic effect was investigated by continuous monitoring in the first 12 days and by Holter monitoring during the 30-day ambulant period and 1 week after discontinuing disopyramide. A significant reappearance of warning arrhythmias could be detected after discontinuing disopyramide sustained-release tablets. No anti-arrhythmic effect was detected in 4 patients. Six patients had to be withdrawn because of side-effects. It is concluded that disopyramide sustained-release tablets 500 mg per day in 2 divided doses gives therapeutic plasma concentrations of 3 mg/l comparable with conventional capsules. A myocardial depressive effect is noted of about 10%.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D002214 Capsules Hard or soft soluble containers used for the oral administration of medicine. Capsule,Microcapsule,Microcapsules
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D004206 Disopyramide A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. Diisopyramide,Disopyramide Monohydrochloride,Disopyramide Phosphate,Disopyramide Phosphate (1:1),Disopyramide Phosphate (1:1), (+-)-Isomer,Disopyramide Phosphate (1:1), (R)-Isomer,Disopyramide Phosphate (1:1), (S)-Isomer,Disopyramide, (+-)-Isomer,Disopyramide, (R)-Isomer,Disopyramide, (S)-Isomer,Disopyramide, D-Tartrate (1:1), (S)-Isomer,Disopyramide, L-Tartrate (1:1), (R)-Isomer,Disopyramide, L-Tartrate (1:1), (S)-Isomer,Disopyramide, L-Tartrate (1:2), (+-)-Isomer,Disopyramide, L-Tartrate, (S)-isomer,Norpace,Palpitin,Palpitine,Rhythmodan,Ritmilen,Rythmilen,SC-13957,SC 13957,SC13957
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D004452 Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Echocardiography, Contrast,Echocardiography, Cross-Sectional,Echocardiography, M-Mode,Echocardiography, Transthoracic,Echocardiography, Two-Dimensional,Transthoracic Echocardiography,2-D Echocardiography,2D Echocardiography,Contrast Echocardiography,Cross-Sectional Echocardiography,Echocardiography, 2-D,Echocardiography, 2D,M-Mode Echocardiography,Two-Dimensional Echocardiography,2 D Echocardiography,Cross Sectional Echocardiography,Echocardiography, 2 D,Echocardiography, Cross Sectional,Echocardiography, M Mode,Echocardiography, Two Dimensional,M Mode Echocardiography,Two Dimensional Echocardiography

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