Format

Send to

Choose Destination
CPT Pharmacometrics Syst Pharmacol. 2016 Mar;5(3):147-57. doi: 10.1002/psp4.12065. Epub 2016 Mar 22.

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

Author information

1
UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill Chapel Hill North Carolina USA.
2
Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill Chapel Hill North Carolina USA.

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 susceptibility decreases, higher doses increase the likelihood of efficacy. With ≥40-fold increases in IC50, IQs suggest alternate regimens be considered. This approach refines previous LPV PK reports, and supports that standard dosing is effective with susceptible virus.

PMID:
27069778
PMCID:
PMC4807435
DOI:
10.1002/psp4.12065
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center