Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration: ACTG Protocol A5143/A5147s Results

J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):510-4. doi: 10.1097/QAI.0000000000000777.

Abstract

This secondary analysis explored changes in protein-unbound concentrations of lopinavir and amprenavir when coadministered in HIV-infected subjects. Total and unbound pharmacokinetic parameters were calculated and compared between subjects receiving each agent alone and coadministration. When coadministered, unbound and total concentrations decrease. Coadministration significantly increased lopinavir unbound clearance, while significant changes in fraction unbound (fu) were not detected. For amprenavir, significant increases in fu and unbound clearance occurred with coadministration. This demonstrates the complex nature of drug-drug interactions between highly protein-bound, CYP-metabolized drugs, and the need to measure unbound concentrations in disease states such as hepatitis C, where such agents are coadministered.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / therapeutic use*
  • Area Under Curve
  • Carbamates / administration & dosage
  • Carbamates / blood
  • Carbamates / pharmacokinetics
  • Carbamates / therapeutic use*
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lopinavir / administration & dosage
  • Lopinavir / blood
  • Lopinavir / pharmacokinetics
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Sulfonamides / administration & dosage
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / therapeutic use*
  • Viral Load

Substances

  • Anti-HIV Agents
  • Carbamates
  • Sulfonamides
  • Lopinavir
  • amprenavir