Atazanavir-bilirubin interaction: a pharmacokinetic-pharmacodynamic model

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 mu mol/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.