VERAPAMIL AND NORVERAPAMIL PLASMA-LEVELS IN INFANTS AND CHILDREN DURING CHRONIC ORAL TREATMENT

Verapamil and norverapamil trough plasma levels were measured in 22 ch ildren, aged from 15 days to 17 years, under chronic oral treatment wi th the drug (mean daily dose +/- SD: 4.9 +/- 1.4 mg/kg) for supraventr icular 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 ve rapamil and 41.7 +/- 28.9 ng/ml for norverapamil. Verapamil and norver apamil trough concentrations were correlated with the daily dose (p < 0.05) but a wide intersubject variability was present at any given dos e and the regression line did not pass through the origin of axes (x-a xis intercept: 1.2 mg/kg for verapamil, 0.9 mg/kg for norverapamil). T o study the influence of age on drug kinetics, verapamil plasma concen trations corrected by daily dose/kg ([V]/D) and norverapamil to verapa mil concentration ratios (N/V) (taken as an index of metabolic clearan ce) were divided according to age quartiles. The median [V]/D was high er in the first and in the fourth age quartile than in the other two a ge groups. On the contrary, median N/V ratio increased with age, sugge sting that drug metabolism was improving during the first year of life . Four children developed typical adverse reactions to the drug (brady cardia, AV block, hypotension). In one case verapamil plasma levels we re definitely high (294 ng/ml). In the other three cases, concomitant factors (such as very young age and heart disease) seem to have contri buted to drug toxicity.