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    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.


    Julie B Dumond, Joseph Rigdon, Katie Mollan, Camlin Tierney, Angela D M Kashuba, Francesca Aweeka, Ann C Collier. Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration: ACTG Protocol A5143/A5147s Results. Journal of acquired immune deficiency syndromes (1999). 2015 Dec 15;70(5):510-4

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    PMID: 26230332

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