Carbamazepine age-dose ratio relationship in children

Steady-state plasma carbamazepine (CBZ) concentrations were measured in 196 pediatric inpatients taking CBZ alone or CBZ combined with other drugs. The steady-state CBZ concentrations divided by the daily administered dose (dose ratio, reciprocal of apparent clearance) increased significantly (r = 0.183, p less than 0.01) with age. The correlation between dose and CBZ concentration, while significant (r = 0.265, p = 0.023), was weak because of wide interindividual differences in dose ratio. There was a negative correlation between CBZ daily dose and CBZ dose ratio. This negative correlation was significant in children 4-6 (r2 = 0.481, p less than 0.01), 7-11 (r2 = 0.399, p less than 0.01), and greater than 11 years of age (r2 = 0.401, p less than 0.01), but not in children less than 4 years of age (r2 = 0.172, p greater than 0.1). The CBZ dose ratio was significantly (p less than 0.001) lower in patients taking CBZ in combination with more than one other antiepileptic drug compared with those on CBZ monotherapy. No significant (p greater than 0.1) difference in CBZ dose ratio was found between male and female patients. These findings suggest that CBZ clearance was influenced by age, dose, and comedication with more than one other antiepileptic drug but not sex. The concentration necessary for efficacy is a clinical, not an analytical decision. However, the dose-concentration relationships show that recommended pediatric CBZ doses of 10-30 mg/kg/day are not enough to attain published therapeutic CBZ concentrations in many children.(ABSTRACT TRUNCATED AT 250 WORDS)