Population pharmacokinetics of imipramine in children

The population pharmacokinetics of imipramine (IMI) and its active metabolite desipramine (DMI) have been evaluated using 177 IMI and DMI serum levels from 49 enuretic children (6-13 y) on IMI treatment. Standard two stage (STS) and maximum likelihood (ML) methods were used to estimate fixed and random effect parameters of IMI. Simultaneous estimation of the drug and metabolite parameters was carried out by the STS method. The mean value of the elimination constant of the drug and metabolite were 0.0425 h-1 and 0.0359, h-1 respectively. Significantly higher variability was found in the pharmacokinetic parameters of the metabolite. According to these estimated pharmacokinetic parameters, the recommended dose for enuretic children should be 1.7 mg.kg-1.day-1. The population pharmacokinetic parameters obtained in the study permit dosage individualisation using a bayesian algorithm.