Determination of phenobarbitone population clearance values for physically and mentally handicapped Chinese children with epilepsy

Abstract

Objective: To estimate population clearance values of phenobarbitone in epileptic children of Chinese origin in Hong Kong.

Method: Steady-state concentration data were gathered during routine care at a special chronic centre for the physically and mentally handicapped. Age, gender, body weight and concurrent medication (taking additional carbamazepine (CBZ) or phenytoin (PTO)) were the four fixed effects tested simultaneously for their influence on the population mean of phenobarbitone clearance, using the nonlinear mixed-effects model.

Results: No age or gender-related effect was found. Both body weight and concurrent medication were the important determinants of phenobarbitone clearance. The population mean values of phenobarbitone clearance obtained were 0.250 litres/day/kg for children on phenobarbitone only and 0.208 litres/day/ kg for those on concomitant CBZ or PTO. Their corresponding interindividual and intraindividual variability values were 34.9% and 15.1% for mono-pharmacy and 29.3% and 7.84% for polypharmacy patient groups.

Conclusion: The correlation between phenobarbitone clearance and body weight found may allow dosage adjustment to be made to achieve target steady-state plasma concentrations.