Abstract |
Verapamil and norverapamil trough plasma levels were measured in 22 children, aged from 15 days to 17 years, under chronic oral treatment with the drug (mean daily dose +/- SD: 4.9 +/- 1.4 mg/kg) for supraventricular tachyarrhythmias (n = 20) or hypertrophic cardiomyopathy (n = 2). Overall, 67 determinations were available (1 to 11 per patient) and the mean concentration values (+/- SD) were 43.3 +/- 36.4 ng/ml for verapamil and 41.7 +/- 28.9 ng/ml for norverapamil. Verapamil and norverapamil trough concentrations were correlated with the daily dose (p < 0.05) but a wide intersubject variability was present at any given dose and the regression line did not pass through the origin of axes (x-axis intercept: 1.2 mg/kg for verapamil, 0.9 mg/kg for norverapamil). To study the influence of age on drug kinetics, verapamil plasma concentrations corrected by daily dose/kg ([V]/D) and norverapamil to verapamil concentration ratios (N/V) (taken as an index of metabolic clearance) were divided according to age quartiles. The median [V]/D was higher in the first and in the fourth age quartile than in the other two age groups. On the contrary, median N/V ratio increased with age, suggesting that drug metabolism was improving during the first year of life. Four children developed typical adverse reactions to the drug ( bradycardia, AV block, hypotension). In one case verapamil plasma levels were definitely high (294 ng/ml). In the other three cases, concomitant factors (such as very young age and heart disease) seem to have contributed to drug toxicity.
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Authors | D Piovan, R Padrini, G Svalato Moreolo, G Magnolfi, O Milanesi, R Zordan, P A Pellegrino, M Ferrari |
Journal | Therapeutic drug monitoring
(Ther Drug Monit)
Vol. 17
Issue 1
Pg. 60-7
(Feb 1995)
ISSN: 0163-4356 [Print] United States |
PMID | 7725379
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Administration, Oral
- Adolescent
- Aging
(metabolism)
- Cardiomyopathy, Dilated
(drug therapy)
- Child
- Child, Preschool
- Female
- Half-Life
- Humans
- Infant
- Infant, Newborn
- Injections, Intravenous
- Male
- Tachycardia, Supraventricular
(drug therapy)
- Verapamil
(administration & dosage, analogs & derivatives, blood, therapeutic use)
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