A pharmacokinetic model of lopinavir in combination with ritonavir in human

摘要

Ritonavir-boosted lopinavir (LPV/r) has been recommended as an alternative regimen for HIV-naive patients who cannot tolerate nevirapine (NVP) and/or efavirenz (EFV). Although combinations of ritonavir and lopinavir have shown higher plasma concentration level of LPV in clinical settings, dosage adjustment is still required to maintain an adequate therapeutic efficacy and reduce side effects. A compartmental pharmacokinetic (PK) model of LPV/r was developed, including a mechanistic description of competitive inhibition. Systematic simulations were performed and predicted plasma drug concentration levels were compared with those from the literature. In particular, the simulated and experimental area under the curve (AUC) based on oral dosing were 76.10 μMol/L, and 76.25 μMol/L, respectively Results from the mathematical model support the hypothesis that the mechanism of LPV/r interaction is due to the competitive inhibition of CYP3A4 in the liver by ritonavir, resulting in an increasing LPV plasma concentration levels. The simulated plasma concentration-time courses were consistent with those from the literature with the goodness of fit (R) of 0.9025 (0.8269–0.9862 95%CI).