Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model

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 th...

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Autores principales:	Lozano R, Domeque N, Apesteguia AF
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/65d59f21e1be470db87d2a3712f6d0fc
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spelling	oai:doaj.org-article:65d59f21e1be470db87d2a3712f6d0fc2021-12-02T06:01:30ZAtazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model1179-1438https://doaj.org/article/65d59f21e1be470db87d2a3712f6d0fc2013-09-01T00:00:00Zhttp://www.dovepress.com/atazanavirndashbilirubin-interaction-a-pharmacokineticndashpharmacodyn-a14510https://doaj.org/toc/1179-1438Roberto 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, pharmacokineticsLozano RDomeque NApesteguia AFDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2013, Iss Issue 1, Pp 153-159 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Lozano R Domeque N Apesteguia AF Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
description	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
format	article
author	Lozano R Domeque N Apesteguia AF
author_facet	Lozano R Domeque N Apesteguia AF
author_sort	Lozano R
title	Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
title_short	Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
title_full	Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
title_fullStr	Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
title_full_unstemmed	Atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
title_sort	atazanavir–bilirubin interaction: a pharmacokinetic–pharmacodynamic model
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/65d59f21e1be470db87d2a3712f6d0fc
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Atazanavir&ndash;bilirubin interaction: a pharmacokinetic&ndash;pharmacodynamic model

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