Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration. (15th December 2015)

• Record Type: Journal Article
• Authors: Dumond, Julie B.; Rigdon, Joseph; Mollan, Katie; Tierney, Camlin; Kashuba, Angela D. M.; Aweeka, Francesca; Collier, Ann C.
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 70:Number 5(2015)
• Publication Date: 2015-12-15
• Subjects: dual protease inhibitor -- lopinavir -- ritonavir -- amprenavir -- unbound concentration -- drug–drug interaction; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000000777
• Languages: English
• ISSNs: 1525-4135

Abstract

Abstract : 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.