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Atazanavir-bilirubin interaction: a pharmacokinetic-pharmacodynamic model
Roberto Lozano1, Nieves Domeque, Alberto-Fermin Apesteguia
1Pharmacy Department, Hospital Real Nuestra, Señora de Gracia.
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.
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