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Bilirubin-A Potential Marker of Drug Exposure in Atazanavir-Based Antiretroviral Therapy

Rekic, Dinko ; Clewe, Oskar ; Roshammar, Daniel ; Flamholc, Leo LU ; Sonnerborg, Anders ; Ormaasen, Vidar ; Gisslen, Magnus ; Abelo, Angela and Ashton, Michael (2011) In AAPS Journal 13(4). p.598-605
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 (I (max)) was estimated at 91% (95% CI, 87-94) and the atazanavir concentration resulting in half of I (max) (IC50) was 0.30 mu mol/L (95%... (More)
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 mu mol/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. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atazanavir, bilirubin, HIV/AIDS, pharmacodynamics, pharmacokinetics
in
AAPS Journal
volume
13
issue
4
pages
598 - 605
publisher
American Association of Pharmaceutical Scientists
external identifiers
  • wos:000297358100008
  • scopus:83555168318
  • pmid:21913053
ISSN
1550-7416
DOI
10.1208/s12248-011-9299-0
language
English
LU publication?
yes
id
3f4283d7-9d73-4284-84a1-581dc0c91f45 (old id 2272686)
date added to LUP
2016-04-01 14:05:13
date last changed
2022-02-19 17:00:24
@article{3f4283d7-9d73-4284-84a1-581dc0c91f45,
  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 (I (max)) was estimated at 91% (95% CI, 87-94) and the atazanavir concentration resulting in half of I (max) (IC50) was 0.30 mu mol/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.}},
  author       = {{Rekic, Dinko and Clewe, Oskar and Roshammar, Daniel and Flamholc, Leo and Sonnerborg, Anders and Ormaasen, Vidar and Gisslen, Magnus and Abelo, Angela and Ashton, Michael}},
  issn         = {{1550-7416}},
  keywords     = {{atazanavir; bilirubin; HIV/AIDS; pharmacodynamics; pharmacokinetics}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{598--605}},
  publisher    = {{American Association of Pharmaceutical Scientists}},
  series       = {{AAPS Journal}},
  title        = {{Bilirubin-A Potential Marker of Drug Exposure in Atazanavir-Based Antiretroviral Therapy}},
  url          = {{http://dx.doi.org/10.1208/s12248-011-9299-0}},
  doi          = {{10.1208/s12248-011-9299-0}},
  volume       = {{13}},
  year         = {{2011}},
}