Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Population pharmacokinetics of ritonavir-boosted saquinavir regimens in HIV-infected individuals
Journal of Antimicrobial Chemotherapy, Volume 62, No. 6, Year 2008
Notification
URL copied to clipboard!
Description
Objectives: The aim of this study was to develop and validate a population pharmacokinetic model in order to describe ritonavir-boosted saquinavir concentrations dosed twice and once daily in human immunodeficiency virus (HIV)-infected patients from the UK, Uganda and Thailand and to identify factors that may influence saquinavir pharmacokinetics. Methods: Pharmacokinetic data from 10 clinical studies were combined. Non-linear mixed effects modelling (NONMEM version V) was applied to determine the saquinavir pharmacokinetic parameters, interindividual/ interoccasion variability (IIV/IOV) and residual error. Various covariates potentially related to saquinavir pharmacokinetics were explored, and the final model was validated by means of 95% prediction interval and testing the predictive performance of the model with data not included in the model-building process. Results: Ninety-seven patients were included from the UK (n = 52), Uganda (n = 18) and Thailand (n = 27), contributing 347 saquinavir profiles (1-14 profiles per patient). A one-compartment model with zero-order absorption and lag-time best described the data with IIV/IOV on apparent oral clearance (CL/F) and volume of distribution (V/F) and with IIV on duration and absorption lag-time. The ritonavir area under the curve over the dosing interval was significantly associated with saquinavir CL/F and V/F. A typical patient from the UK had ∼1.5- and 3-fold higher saquinavir CL/F compared with patients from Uganda (89.0 versus 49.8 L/h) and Thailand (89.0 versus 26.7 L/h), respectively. Conclusions: A model to characterize ritonavir-boosted saquinavir pharmacokinetics in HIV-infected adults has been developed and validated. The model could be used for dosage adaptation following therapeutic drug monitoring and to assess patients' suitability for once-daily boosted saquinavir therapy. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Dickinson, Laura
United Kingdom, Liverpool
Liverpool University Hospitals Nhs Foundation Trust
United Kingdom, Liverpool
University of Liverpool
Boffito, Marta A.
United Kingdom, London
Chelsea and Westminster Foundation Trust
Back, David J.
United Kingdom, Liverpool
University of Liverpool
Khoo, Saye Hock
United Kingdom, Liverpool
University of Liverpool
Pozniak, Anton Louis
United Kingdom, London
Chelsea and Westminster Foundation Trust
Mugyenyi, Peter N.
Uganda, Kampala
Joint Clinical Research Center Uganda
Merry, Concepta
Ireland, Dublin
Trinity College Dublin
Autar, R. S.
Thailand, Bangkok
The Hiv Netherlands Australia Thailand Research Collaboration
Burger, David M.
Netherlands, Nijmegen
Radboud University Medical Center
Aarons, Leon
United Kingdom, Manchester
The University of Manchester
Statistics
Citations: 13
Authors: 10
Affiliations: 8
Identifiers
Doi:
10.1093/jac/dkn399
ISSN:
03057453
e-ISSN:
14602091
Research Areas
Cancer
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
Uganda