Steady-State Carbamazepine Plasma Concentration-Dose Ratios in Epileptic Patients

Abstract

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.

Carbamazepine Clearance in Paediatric Epilepsy Patients

“…From later work (Elyas et al 1986;Riva et al 1985;Sanchez et al 1986) and the results presented in the present article it now seems highly unlikely that the pharmacokinetics of carbamazepine in children are comparable with those in adults. A negative relationship between carbamazepine clearance and body mass (r = -0.87) is clearly shown here.…”

“…The auto-induction is due to induction of the epoxide-diol pathway (Eichelbaum et al 1985). Sanchez et al (1986) also observed dose-dependent pharmacokinetics. There is inconclusive evidence that carbamazepine absorption is impaired at high doses, so that it can be surmised that the decrease in the rate of rise of plasma concentration with increased dose may be due to an increased clearance.…”

“…The difference in clearance between the lowest and the highest mass group is highly significant (p = 0.0001 for MT and p = 0.003 for CT). Similarly, Sanchez et al (1986) found that the plasma concentration/dose ratio increased with increasing age. Elyas and co-workers (1986) found a negative correlation (r = -0.49) between age and total carbamazepine-10, II-epoxide: carbamazepine ratio in 68 children whose ages ranged from 3 months to 19.5 years [mean = 11.8 (± 4.5) years], which implied decreasing clearance with increasing age.…”

“…The effect of age and/or dose on the pharmacokinetics of carbamazepine is still not clear (Battino et al 1980;Furlanut et al 1985;Kumps 1981;Kumps & Mardens 1983;Pynnonen et al 1977;Rane et al 1976;Rey et al 1979;Riva et al 1985;Sanchez et al 1986). The effect of age and/or dose on the pharmacokinetics of carbamazepine is still not clear (Battino et al 1980;Furlanut et al 1985;Kumps 1981;Kumps & Mardens 1983;Pynnonen et al 1977;Rane et al 1976;Rey et al 1979;Riva et al 1985;Sanchez et al 1986).…”

“…It is also used in the treatment of trigeminal neuralgia and tabetic lightning pains (Rane et al 1976). The pharmacokinetics of the drug and its active metabolite carbamazepine-IO,II-epoxide have been studied extensively in adults and to some extent in children (Eadie & Tyrer 1980;Morselli & Bossi 1982;Morselli et al 1975), but few studies on large numbers of children have been reported (Battino et al 1980;Furlanut et al 1985;Rane et al 1976;Sanchez et al 1986). Most of these considered the plasma concentration/dose ratio in Caucasian children.…”