Bilirubin—A Potential Marker of Drug Exposure in Atazanavir-Based Antiretroviral Therapy
Journal Title: The AAPS Journal - Year 2011, Vol 13, Issue 4
Abstract
The objective of this work was to examine the atazanavir–bilirubin relationship using a population-based approach and to assess the possible application of bilirubin as a readily available marker of atazanavir exposure. A model of atazanavir exposure and its concentration-dependent effect on bilirubin levels was developed based on 200 atazanavir and 361 bilirubin samples from 82 patients receiving atazanavir in the NORTHIV trial. The pharmacokinetics was adequately described by a one-compartment model with first-order absorption and lag-time. The maximum inhibition of bilirubin elimination rate constant (Imax) was estimated at 91% (95% CI, 87–94) and the atazanavir concentration resulting in half of Imax (IC50) was 0.30 μmol/L (95% CI, 0.24–0.37). At an atazanavir/ritonavir dose of 300/100 mg given once daily, the bilirubin half-life was on average increased from 1.6 to 8.1 h. A nomogram, which can be used to indicate suboptimal atazanavir exposure and non-adherence, was constructed based on model simulations.
Authors and Affiliations
Dinko Rekić, Oskar Clewe, Daniel Röshammar, Leo Flamholc, Anders Sönnerborg, Vidar Ormaasen, Magnus Gisslén, Angela Äbelö, Michael Ashton
Keywords
Related Articles
- EP ID EP681344
- DOI 10.1208/s12248-011-9299-0
- Views 72
- Downloads 0
Efficacious Intestinal Permeation Enhancement Induced by the Sodium Salt of 10-undecylenic Acid, A Medium Chain Fatty Acid Derivative
The online version of this article (doi:10.1208/s12248-014-9634-3) contains supplementary material, which is available to authorized users.
Holford NHG and Sheiner LB “Understanding the Dose-Effect Relationship-Clinical Application of Pharmacokinetic-Pharmacodynamic Models”, Clin Pharmacokin 6:429–453 (1981)—The Backstory
Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations
Metrics are discussed which are used for the evaluation of bioequivalence of modified-release formulations. In order to ensure the therapeutic equivalence of the compared drug products, it would be important to contrast...
MicroPET investigation of chronic long-term neurotoxicity from heavy ion irradiation
Positron emission tomography (PET) permits imaging of the regional biodistribution and pharmacokinetics of compounds labeled with short-lived positron-emitting isotopes. It has enabled evaluation of neurochemical systems...
Evaluation of the antioxidant activity of different flavonoids by the chemiluminescence method
The objective of the present investigation was to study the antioxidant action of different flavonoids (quercetin, glabridin, red clover, and Isoflavin Beta, an isoflavones mixture) in order to determine if they could be...