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JAC Advance Access originally published online on October 4, 2005
Journal of Antimicrobial Chemotherapy 2005 56(5):908-913; doi:10.1093/jac/dki354
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in Thai and UK patients

Reshma Saskia Autar1,2,*, Marta Boffito3, Elly Hassink2, Ferdinand W. N. M. Wit2, Jintanat Ananworanich1, Umaporn Siangphoe1, Anton Pozniak3, David A. Cooper1,4, Praphan Phanuphak1,5, Joep M. A. Lange1,2, Kiat Ruxrungtham1,5 and David M. Burger6

1 The HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross Aids Research Centre (TRCARC), Bangkok, 104 Rajdumri Road, 10330 Pathumwan, Bangkok, Thailand; 2 International Antiviral Therapy Evaluation Center (IATEC), Center for Poverty-related Communicable Diseases, Department of Internal Medicine, Academic Medical Center (AMC), University of Amsterdam (UVA), Pietersbergweg 9, 1105 BM, Amsterdam, The Netherlands; 3 Chelsea and Westminster Hospital, 369 Fulham Road, SW10 9NH, London, UK; 4 National Center in HIV Epidemiology and Clinical Research, 376 Victoria Street, Sydney NSW 2010, Australia; 5 Department of Medicine, Faculty of Medicine, King Chulalongkorn University, 1873 Rama IV Road, Phathumwan, 10330, Bangkok, Thailand; 6 Radboud University Medical Center, Geert Grooteplein 8, 6525 GA, Nijmegen, The Netherlands

Received 4 June 2005; returned 24 July 2005; revised 24 August 2005; accepted 8 September 2005

* Correspondence address. The HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross Aids Research Centre (TRCARC), 104 Rajdumri Road, 10330 Pathumwan, Bangkok, Thailand. Tel: +66-2255-7334; Fax: +66-2252-5779; E-mail: saskia{at}hivnat.com

Objectives: Differential exposure to saquinavir/ritonavir may lead to therapy failure. The objective was to identify factors that influence variability of saquinavir/ritonavir plasma concentrations.

Methods: Saquinavir/ritonavir data, dosed as 1600/100 mg once daily, from three separate pharmacokinetic studies, in 45 patients from Thailand and the UK, were pooled. Pharmacokinetic parameters were based on non-compartmental analysis. Univariate analysis was performed with saquinavir as the dependent variable, and ritonavir area under the curve (AUC), gender, body weight, body mass index (BMI) and study site as independent variables. Variables with a P value <0.10 were included in a multivariate linear regression analysis.

Results: Higher saquinavir AUCs, maximum concentrations (Cmax) and minimum concentrations (Cmin) were seen in Thai patients than in UK patients. Univariate analysis showed associations between body weight, gender, study site and ritonavir AUC and saquinavir AUC (P < 0.05), whereas BMI (P = 0.13) did not. In the multivariate analysis, ritonavir AUC (P = 0.0001) and study site (P = 0.0021) were significantly related to saquinavir AUC (R2 = 0.50).

Conclusions: The ritonavir AUC and study site appeared to be related to exposure of saquinavir. Study site should be viewed as the total of country- and study-specific differences—such as differences in lifestyle, environment, genetic background and dietary composition—between the analysed studies.

Keywords: HIV , clinical pharmacology , protease inhibitors , Thailand , United Kingdom


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