Relationship between the therapeutic effects or side-effects and the serum disopyramide or mono-N-dealkylated disopyramide concentration after repeated oral administration of disopyramide to arrhythmic patients.
After we had developed a method to determine simultaneously the blood concentrations of disopyramide (DP) and its metabolite mono-N-dealkylated disopyramide (MND) by high-performance liquid chromatography, DP was administered repeatedly to arrhythmic patients in order to examine the relationship between the serum DP or MND concentration and the therapeutic effects or side-effects. To 79 arrhythmic patients (57 patients with ventricular premature contraction, 13 with supraventricular arrhythmia and 9 with atrial fibrillation), DP was administered repeatedly at an initial oral dose of 200 to 400 mg/day. Of the 61 patients which were possible to evaluate after reaching a steady state, 32 were evaluated as effective and 29 as non-effective, the effective rate being 52.5%; the mean blood DP concentration (+/- S.D.) was 2.14 +/- 0.65 and 1.74 +/- 0.62 micrograms/ml, respectively, with a significant difference between the two groups (p +/- 0.05). At the final dose, 40 patients were evaluated as effective and 18 as non-effective, the effective rate being 69.0%; the mean blood DP concentration was 2.03 +/- 0.67 and 2.09 +/- 0.68 micrograms/ml, respectively, with no significant difference between the two groups. Among 42 patients with premature contraction, 26 were evaluated as effective and 16 as non-effective, the effective rate being 62%; the mean blood DP concentration was 2.01 +/- 0.62 and 2.20 +/- 0.70 micrograms/ml respectively, with no significant difference between the two groups. The incidence of side-effects was 17.7%, and there were no significant differences in blood DP or MND concentrations between the groups with and without side-effects. A blood DP concentration more than 2 micrograms/ml may be required to achieve the therapeutic effect of DP administered repeatedly.
Masuhara
K
K
Department of Pharmacy, St. Marianna University, Kanagawa, Japan.
Ohno
T
T
Hamaguchi
K
K
Katoh
K
K
Kashiwada
K
K
Takahashi
S
S
Tanaka
Y
Y
Someya
K
K
Ogata
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D004206:Disopyramide / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000889:Anti-Arrhythmia Agents; D004206:Disopyramide