title: Indinavir plasma protein binding in HIV-1-infected adults.
abstract: OBJECTIVE
  To quantify unbound indinavir concentrations and characterize indinavir plasma protein binding in HIV-infected adults.
  
  
  METHODS
  Pharmacokinetic study in antiretroviral-naive, HIV-infected persons with CD4 T lymphocytes > 100 x 10(6) cells/L and HIV-RNA in plasma >5000 copies/ml at baseline who were participating in an open-label study of zidovudine, lamivudine and indinavir therapy.
  
  
  METHODS
  Eight men underwent 8 h intensive pharmacokinetic studies for indinavir on two occasions 6 months apart. Unbound indinavir was separated by ultra-filtration, and unbound and total concentrations were quantified by a validated high-performance liquid chromatography method.
  
  
  RESULTS
  Overall indinavir protein binding was 61+/-6%, with a range among the profiles of 54 to 70%. Indinavir binding was higher at the 8 h post-dose concentration compared with the 1 h post-dose concentration (66 versus 57%, P = 0.0006).
  
  
  CONCLUSIONS
  The mean 61% protein binding for indinavir in these HIV-infected persons is similar to the in vitro report of 60%. However, the fraction bound was concentration-dependent, and considerable variability in binding was present among patients. Quantification of unbound protease inhibitor concentrations opens new avenues of research to advance our understanding of the pharmacologically-relevant moieties of antiretroviral agents and thereby the pharmacotherapy of HIV infection.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Anderson
authors.forename: R C
authors.initials: RC
authors.lastname: Brundage
authors.forename: L
authors.initials: L
authors.lastname: Bushman
authors.forename: T N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: R P
authors.initials: RP
authors.lastname: Remmel
authors.forename: C V
authors.initials: CV
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D017320:HIV Protease Inhibitors; D019469:Indinavir