Open AccessModel‐Based Analysis of Unbound Lopinavir Pharmacokinetics in HIV‐Infected Pregnant Women Supports Standard Dosing in the Third Trimester
Author(s) -
Chen J,
Malone S,
Prince HMA,
Patterson KB,
Dumond JB
Publication year - 2016
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12065
Subject(s) - lopinavir , dosing , pharmacokinetics , lopinavir/ritonavir , pregnancy , ritonavir , medicine , pharmacology , population , human immunodeficiency virus (hiv) , viral load , virology , biology , antiretroviral therapy , environmental health , genetics
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 IC 50 . As viral susceptibility decreases, higher doses increase the likelihood of efficacy. With ≥40‐fold increases in IC 50 , IQs suggest alternate regimens be considered. This approach refines previous LPV PK reports, and supports that standard dosing is effective with susceptible virus.