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Bilirubin-a potential marker of drug exposure in atazanavir-based antiretroviral therapy.

Journal article
Authors Dinko Rekić
Oskar Clewe
Daniel Röshammar
Leo Flamholc
Anders Sönnerborg
Vidar Ormaasen
Magnus Gisslén
Angela Abelö
Michael Ashton
Published in The AAPS journal
Volume 13
Issue 4
Pages 598-605
ISSN 1550-7416
Publication year 2011
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Institute of Biomedicine, Department of Infectious Medicine
Pages 598-605
Language en
Subject categories Pharmacy, Clinical pharmacology, Pharmaceutical pharmacology, Infectious Medicine


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 (I (max)) was estimated at 91% (95% CI, 87-94) and the atazanavir concentration resulting in half of I (max) (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.

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