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

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

Author information

1
*UNC Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC; †Gillings School of Global Public Health, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC; ‡School of Medicine, Department of Internal Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC; §Center for AIDS Research, Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC; ‖Center for Biostatistics in AIDS Research, The Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA; ¶UCSF School of Pharmacy, Department of Clinical Pharmacy, San Francisco, CA; and #University of Washington School of Medicine, Division of Allergy and Infectious Diseases, Seattle, WA.

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.

PMID:
26230332
PMCID:
PMC4648657
DOI:
10.1097/QAI.0000000000000777
[Indexed for MEDLINE]
Free PMC Article

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