Back to Journals » Clinical Pharmacology: Advances and Applications » Volume 5 » Issue 1

Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model

Authors Lozano R, Domeque N, Apesteguia A

Received 15 May 2013

Accepted for publication 16 July 2013

Published 27 September 2013 Volume 2013:5(1) Pages 153—159

DOI https://doi.org/10.2147/CPAA.S48377

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3


Roberto Lozano,1 Nieves Domeque,2 Alberto-Fermin Apesteguia3

1Pharmacy Department, 2Psychiatry Department, Hospital Real Nuestra Señora de Gracia, 3Pharmacy Department, Hospital Clinico Universitario "Lozano Blesa", Zaragoza, Spain

Purpose: The aim of this work was to analyze the atazanavir–bilirubin relationship, using a new mathematical approach to pharmacokinetic–pharmacodynamic models, for competitive drug interactions based on Michaelis–Menten equations.
Patients and methods: Because atazanavir induces an increase of plasma bilirubin levels, in a concentration-dependent manner, we developed a mathematical model, based on increments of atazanavir and bilirubin concentrations at steady state, in HIV infected (HIV+) patients, and plotted the corresponding nomogram for detecting suboptimal atazanavir exposure.
Results: By applying the obtained model, the results indicate that an absolute value or an increment of bilirubin at steady state below 3.8 µmol/L, are predictive of suboptimal atazanavir exposure and therapeutic failure.
Conclusion: We have successfully implemented a new mathematical approach to pharmacokinetic–pharmacodynamic model for atazanavir–bilirubin interaction. As a result, we found that bilirubin plasma levels constitute a good marker of exposure to atazanavir and of viral suppression.

Keywords: atazanavir, bilirubin, HIV/AIDS, pharmacodynamics, pharmacokinetics

Corrigendum for this paper has been published.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]