title: Brief Report: Significant Decreases in Both Total and Unbound Lopinavir and Amprenavir Exposures During Coadministration: ACTG Protocol A5143/A5147s Results.
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.
authors.affiliation: *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.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Dumond
authors.forename: Joseph
authors.initials: J
authors.lastname: Rigdon
authors.forename: Katie
authors.initials: K
authors.lastname: Mollan
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D019540:Area Under Curve; D002219:Carbamates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir