PurposeThe 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 methodsBecause 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.ResultsBy 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.ConclusionWe 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.

The objective of the present work was to conduct an "in vivo" analysis of the atazanavir-bilirubin interaction. We developed a new mathematical approach to PK/PDPK models for competitive interaction based on the Michaelis-Menten equation, which was applied to patients with polymorphisms in the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1). Atazanavir is known to induce concentration-dependent increases in bilirubin plasma levels. Thus, we employed our mathematical model to analyse rises in steady state atazanavir and bilirubin concentrations, ultimately plotting a nomogram for detection of suboptimal atazanavir exposure. Application of our model revealed that an absolute value or a steady state increase in bilirubin falling below 3.8Φ µmol/L (where Φ is a correction factor, =1 for UGT1A1 wild type and ≠1 for UGT1A1 variants) could be used to predict suboptimal atazanavir exposure and treatment failure. Thus, we have successfully established a new mathematical approach for pharmacodynamic-pharmacokinetic modelling of the interaction between atazanavir and bilirubin, as it relates to genetic variants of UGT1A1. Taken together, our findings indicate that bilirubin plasma levels represent a valuable marker of atazanavir exposure.

Publish your work in this journalSubmit your manuscript here: http://www.dovepress.com/clinical-pharmacology-advances-and-applications-journal Clinical Pharmacology: Advances and Applications is an international, peer-reviewed, open access journal publishing original research, reports, reviews and commentaries on all areas of drug experience in humans. The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. where V = glucuronidation reaction rate for bilirubin and ATZ, respectively; E o = UGT1A1 enzyme concentration; K m = Michaelis-Menten's constant for bilirubin and ATZ, respectively; and K cat = turnover number for bilirubin and ATZ, respectively."Clinical Pharmacology: Advances and Applications downloaded from https: //www.dovepress.com/ by 34.208.6.16 on 10-May-2018 For personal use only.Powered by TCPDF (www.tcpdf.org)

Aim: To identify the drug class and/or duration of treatments causing hyposideremia. Study Design: Retrospective case-control study. Place and Duration of Study: Departments of Internal Medicine and Pharmacy, Aragón Health Services Services Hospital Real de Nuestra Señora de Gracia, between January 2019 and December 2019. Methodology: The records of prescripted medicines of all patients admitted to Internal Medicine  service, for various indications, along a 1-year period (2019), which were  ultimately analized according to association with hyposideremia. Results: It was identified several drugs associated with low plasma iron levels: acetylcysteine and apixaban, which would increase the risk of hyposideremia. On the contrary, we found that allopurinol, duloxetine and simvastatin would protect against the appearance of hyposideremia. Conclusion: Acetylcysteine and apixaban, alone or in combination with different pathologies, would be capable of inducing, and on dependence of the duration of treatment and/or of the concomitant pathology, hyposideremia, iron deficiency and, in certain cases, anemia constituting a major health problem.

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