Prediction of steady-state verapamil plasma concentrations in children and adults

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Abstract
The average steady-state plasma verapamil concentration in subjects on long-term oral therapy of 80 mg every 6 h (Y) correlated strongly with the area under the curve from zero to infinity [AUC0-.infin./6 (X), where the area refers to that for a single oral dose of 80 mg (.cxa.Y = 2.41X, n = 15, r = 0.923, P < 0.001)]. Steady-state concentrations are predictable from the single-dose data, with an average absolute deviation of 11.1%. Seven children (7-19 yr old) were given an initial i.v. bolus dose of 0.1 mg/kg, followed by a 20-min constant rate infusion of 0.007 mg/kg per min. At 24 h after the bolus dose they were put on oral therapy (40-80 mg every 6 h) and 1 mo. later the minimum steady-state verapamil plasma concentration .**GRAPHIC**. was measured. Plasma concentration-time data obtained after the infusion were fitted to biexponential (2 sets) or triexponential equations (5 sets). The coefficients of the postinfusion polyexponential equations were converted to those for 0.1-mg/kg bolus dose alone. Mean parameters estimated were as follows: plasma clearance 0.500 l/min; steady-state volume of distribution 279 l; V.beta. 394 l; half-life 9.17 h; and mean residence time 10.0 h. Many correlations were made between the oral .**GRAPHIC**. values and functions obtained from the i.v. data. The best correlation was that between .**GRAPHIC**. and the predicted steady-state concentration at 3 h after dosing when bolus doses would be given at 6-h intervals based on the single-dose i.v. data (r = 0.985, P < 0.001); this correlation allowed .**GRAPHIC**. to be predicted with an average absolute deviation of 10%. Norverapamil was measured in plasma after oral dosing, but was not detectable after i.v. dosing. [Verapamil is used in the treatment of various cardiovascular conditions.].

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