Model-Based Analysis of Unbound Lopinavir Pharmacokinetics in HIV-Infected Pregnant Women Supports Standard Dosing in the Third Trimester.

ABSTRACT: Physiological changes during pregnancy can affect drug pharmacokinetics. Here we present a population pharmacokinetic model to describe the longitudinal change of unbound lopinavir/ritonavir (LPV/RTV) PK parameters with gestational age, and to predict unbound LPV concentrations under different dosing regimens. The changes in apparent intrinsic clearances of LPV and RTV during pregnancy are described using an exponential function of gestational age. The unbound fractions of LPV/RTV are not significantly different between pregnancy and postpartum. Simulation reveals that despite increases in LPV intrinsic clearance, effective LPV inhibitory quotient (IQ) values are predicted with the standard dosing (400/100 mg b.i.d.) in >90% of simulations, with ≤4-fold increase in viral IC50. As viral sus

SUBMITTER: Chen J 

PROVIDER: S-EPMC4807435 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature