Compartmental pharmacokinetic modeling of lopinavir in humans

摘要

Background: Lopinavir is a highly potent protease inhibitors commonly used in treatment of HIV infection. The drug has a very low bioavailability due to a rapid metabolism by cytochrome P450 3A (CYP3A) isoenzyme. We aimed to develop a biologically relevant pharmacokinetic model of lopinavir with a description of a CYP3A4-mediated first pass metabolism and enterohepatic circulation (EHC). Methods: A theoretical model of lopinavir was developed using the classical pharmacokinetic modeling concept. The model consisted of one compartment with first-order absorption from gastrointestinal (GI) depot and first-order clearance into recycling depot which incorporated into the model structure using ACSLX. Results: Lopinavir plasma concentration-time course was successfully simulated against a dataset from the literature. The model had an absorption rate constant (K