Assessment of lopinavir pharmacokinetics with respect to developmental changes in infants and the impact on weight band-based dosing.

Improved antiretroviral therapies are needed for the treatment of HIV infected infants due to rapid disease progression and drug resistance from perinatal exposure to antiretrovirals. We examined longitudinal pharmacokinetic (PK) data from a clinical trial of lopinavir/ritonavir in HIV-infected infants initiating therapy less than 6 months of age. A population PK analysis was performed using NONMEM to characterize changes in lopinavir (LP V) PK relating to maturational changes in infants, and to assess dosing requirements in this population. We also investigated the relationship between LPV PK and viral dynamic response. Age and ritonavir concentrations were the only significant covariates found. Population PK of LPV was characterized by high apparent clearance in young infants which decreased with age. Although younger infants had lower LPV concentrations, viral dynamics did not correlate with initial LPV exposure. Monte Carlo simulations demonstrated that WHO weight band-based dosing recommendations predicted therapeutic LPV concentrations and provided comparable drug exposure levels comparable to those resulting from US Food and Drug Administration (FDA)-suggested dosing regimens.