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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


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

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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.

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