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

TitleBrief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration: ACTG Protocol A5143/A5147s Results.
Publication TypeJournal Article
Year of Publication2015
AuthorsDumond JB, Rigdon J, Mollan K, Tierney C, Kashuba ADM, Aweeka F, Collier AC
JournalJ Acquir Immune Defic Syndr
Volume70
Issue5
Pagination510-4
Date Published2015 Dec 15
ISSN1944-7884
KeywordsAdult, Anti-HIV Agents, Area Under Curve, Carbamates, Drug Interactions, Drug Therapy, Combination, Female, HIV Infections, Humans, Lopinavir, Male, Middle Aged, Sulfonamides, Viral Load
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.

DOI10.1097/QAI.0000000000000777
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID26230332
PubMed Central IDPMC4648657
Grant ListAI068634 / AI / NIAID NIH HHS / United States
K23 AI093156 / AI / NIAID NIH HHS / United States
K23AI093156 / AI / NIAID NIH HHS / United States
M01 RR000046 / RR / NCRR NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI50410 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069481 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1AI068636 / AI / NIAID NIH HHS / United States
UM1AI069481 / AI / NIAID NIH HHS / United States