A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens.
The distribution of carbamazepine plasma concentration-dose ratio was studied in 322 samples from patients undergoing long term treatment. Data have been grouped according to: age--3 to 6, 7 to 9, 10 to 14, and above 15 years old; number of drugs used in the treatment--mono- and polytherapy; dose--less than or equal to 10, 10.1 to 14.9, 15 to 19.9, and greater than or equal to 20 mg/kg; and plasma concentration found--less than 4, 4 to 8, 8.1 to 12, and greater than 12 mg/L. From the results it is concluded that the carbamazepine concentration-dose ratio increases with age in children, but is less than in adults, is higher in monotherapy than in polytherapy, and decreases as the dose increases.
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