Bilirubin-A Potential Marker of Drug Exposure in Atazanavir-Based Antiretroviral Therapy
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2272686
- author
- Rekic, Dinko ; Clewe, Oskar ; Roshammar, Daniel ; Flamholc, Leo LU ; Sonnerborg, Anders ; Ormaasen, Vidar ; Gisslen, Magnus ; Abelo, Angela and Ashton, Michael
- organization
- publishing date
- 2011
- 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}}, }