Population Analysis of Weight-, Age-, and Sex-Related Differences in the Pharmacokinetics of Lopinavir in Children from Birth to 18 Years

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Abstract
The pharmacokinetics of lopinavir were investigated by the use of a population approach performed with the nonlinear mixed effect modeling program NONMEM and 157 children ranging in age from 3 days to 18 years. The pharmacokinetics of lopinavir were well described by a one-compartment model in which the absorption and the elimination rate constants were equal. Typical population estimates of the apparent volume of distribution ( V / F ) and plasma clearance (CL/ F ) were 24.6 liters and 2.58 liters/h, respectively. The lopinavir V / F and CL/ F were both related to body weight (BW), with an important increase in weight-normalized CL/ F for the lowest BW. Combined treatment with lopinavir and nevirapine was found to increase the CL/ F . The lopinavir CL/ F was also age and sex related, as a 39% increase was observed after the age of 12 years for boys compared to the CL/ F for girls. The consequences of these pharmacokinetic discrepancies and the necessity to modify the currently recommended dosage regimen should be further investigated.