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Protein binding of lopinavir and ritonavir during 4 phases of pregnancy: implications for treatment guidelines

Kristine B Patterson1, Julie B Dumond, Heather A Prince

  • 1Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-7215, USA. kristine_patterson@med.unc.edu

Journal of Acquired Immune Deficiency Syndromes (1999)
|December 11, 2012
PubMed

Insights

This study found that while total lopinavir/ritonavir (LPV/RTV) exposure decreased during pregnancy, unbound LPV/RTV levels remained stable. This suggests that dose adjustments may not be necessary for all HIV-infected pregnant women.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Infectious Diseases and Virology
  • Maternal-Fetal Medicine

Background:

  • Pregnancy significantly alters drug pharmacokinetics (PKs), potentially impacting antiretroviral therapy efficacy in HIV-infected women.
  • Lopinavir/ritonavir (LPV/RTV) is a crucial component of antiretroviral regimens, but its PK profile during pregnancy requires careful consideration.
  • Understanding changes in both total and unbound drug concentrations is essential for optimizing treatment outcomes.

Purpose of the Study:

  • To investigate the intraindividual pharmacokinetics (PKs) of total and unbound lopinavir/ritonavir (LPV/RTV) during pregnancy.
  • To assess if the pediatric formulation of LPV/RTV can mitigate pregnancy-associated PK changes.
  • To determine if LPV/RTV dose adjustments are necessary for HIV-infected pregnant women.

Main Methods:

  • A prospective longitudinal PK study was conducted in HIV-infected pregnant women.
  • Participants received standard LPV/RTV (400 mg/100 mg) twice daily, with dose escalation using the pediatric formulation (100 mg/25 mg) at 30 weeks gestation.
  • Intensive PK evaluations were performed at multiple time points: 20-24 weeks, 30 weeks, 32 weeks, and 8 weeks postpartum.

Main Results:

  • Total LPV exposure (AUC0-12h) was significantly lower during pregnancy compared to postpartum (P = 0.005).
  • Unbound LPV AUC0-12h remained unchanged throughout pregnancy, even after a 25% dose increase.
  • Unbound LPV predose concentrations (C12h) were not significantly affected by the dose increase and remained well above the minimum efficacy concentration.

Conclusions:

  • Total LPV exposure decreases during pregnancy, but unbound LPV exposure remains stable.
  • The pediatric formulation did not significantly alter unbound LPV concentrations, suggesting it may not be necessary for all pregnant women.
  • Current dosing of LPV/RTV may be adequate for maintaining therapeutic unbound concentrations in most HIV-infected pregnant women.
Abstract

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