Comparative Pharmacokinetic Study of Chewable and Conventional Carbamazepine in Children

Abstract

Fifteen children (7 boys and 8 girls) with generalized tonic-clonic seizures (GTCS) and partial seizures with elementary or complex symptomatology, treated with carbamazepine (CBZ) alone (n = 7) or in combination with either phenobarbital (PB, n = 6) or clobazam (CLB, n = 2) given for at least 3 months at stable individualized doses and regimens, entered an open, within-patient, change-over study of consecutive periods, each lasting 2 weeks. During period 1, conventional CBZ was given; during period 2, a chewable CBZ formulation was substituted for conventional CBZ and given at the same total daily dosage with the same schedule as in period 1. Blood samples for measuring plasma concentration of both total CBZ and CBZ-10,11 epoxide (CBZ-E) were taken on the last day of each period. No significant difference between the two periods was noted in the mean +/- SD of Cmax, Css mean, and area under the curve (AUC) of total CBZ and CBZ-E. The two different CBZ formulations, administered at the same total daily dosage, can be considered bioequivalent.

Medication Choices for Paediatric Epilepsy

“…However, the significance of some of these effects on the clinical effectiveness of CBZ remains unclear [2]. Carbamazepine is a water insoluble drug and absorption rate varies according to formulation types [41]. It is well distributed in the body tissues and approximately 75% of carbamazepine binds to plasma proteins.…”

“…It is well distributed in the body tissues and approximately 75% of carbamazepine binds to plasma proteins. It is metabolised by cytochrome P450 enzymes to carbamazepine -10,11-epoxide (active metabolite) in the liver [41] and is more rapidly metabolised in infants [2]. Thus, CBZ activity and toxicity are higher in infants and younger children.…”