Indinavir plasma protein binding in HIV-1-infected adults

P. L. Anderson, R. C. Brundage, L. Bushman, T. N. Kakuda, R. P. Remmel, Courtney V Fletcher

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Objective: To quantify unbound indinavir concentrations and characterize indinavir plasma protein binding in HIV-infected adults. Design: Pharmacokinetic study in antiretroviral-naive, HIV-infected persons with CD4 T lymphocytes > 100 x 106 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. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)2293-2297
Number of pages5
JournalAIDS
Volume14
Issue number15
DOIs
StatePublished - Nov 23 2000

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Indinavir
Protein Binding
HIV-1
Blood Proteins
HIV
Pharmacokinetics
Anti-Retroviral Agents
Lamivudine
Zidovudine
Protease Inhibitors
HIV Infections
High Pressure Liquid Chromatography
RNA
T-Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Anderson, P. L., Brundage, R. C., Bushman, L., Kakuda, T. N., Remmel, R. P., & Fletcher, C. V. (2000). Indinavir plasma protein binding in HIV-1-infected adults. AIDS, 14(15), 2293-2297. https://doi.org/10.1097/00002030-200010200-00010

Indinavir plasma protein binding in HIV-1-infected adults. / Anderson, P. L.; Brundage, R. C.; Bushman, L.; Kakuda, T. N.; Remmel, R. P.; Fletcher, Courtney V.

In: AIDS, Vol. 14, No. 15, 23.11.2000, p. 2293-2297.

Research output: Contribution to journalArticle

Anderson, PL, Brundage, RC, Bushman, L, Kakuda, TN, Remmel, RP & Fletcher, CV 2000, 'Indinavir plasma protein binding in HIV-1-infected adults', AIDS, vol. 14, no. 15, pp. 2293-2297. https://doi.org/10.1097/00002030-200010200-00010
Anderson PL, Brundage RC, Bushman L, Kakuda TN, Remmel RP, Fletcher CV. Indinavir plasma protein binding in HIV-1-infected adults. AIDS. 2000 Nov 23;14(15):2293-2297. https://doi.org/10.1097/00002030-200010200-00010
Anderson, P. L. ; Brundage, R. C. ; Bushman, L. ; Kakuda, T. N. ; Remmel, R. P. ; Fletcher, Courtney V. / Indinavir plasma protein binding in HIV-1-infected adults. In: AIDS. 2000 ; Vol. 14, No. 15. pp. 2293-2297.
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