Abstract
Although intravenous verapamil effectively terminates supraventricular tachycardia (SVT) in children, its utility as a chronic oral antidysrhythmic drug has been disappointing. To assess whether drug kinetics contribute to this problem, we measured serum concentrations before and for 24 hours after a maintenance oral dose of verapamil (mean dose 1.36 mg/kg, range 0.4-2.9 mg/kg) in 7 children with a median age of 10.8 yrs (range 2.8-15.3 yrs). All had SVT controlled by chronic oral verapamil at mean serum peak and trough concentrations of 248±117 and 64±38 ng/ml, respectively. We found several clearly age-dependent kinetic parameters: younger children demonstrated faster drug uptake “Tmax” (p <.005), lower relative bioavailability “F” (p<.01), smaller volume of distribution “Vd” (p <.005) and slower elimination half-life “t ½ β” (p <.001). Younger children also exhibited a possible diurnal variation in drug kinetics. There was no significant age-relationship in distribution half-life “t½α” or drug clearance rate. Although these changes have opposing effects on serum concentrations, their net effect in young children is for a greater dosage requirement, and perhaps a shorter dosage interval, than are currently recommended. *Supported in part by G.D. Searle & Co. of Canada, Ltd., and the Ontario Heart and Stroke Foundation.
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