Articles
Clinical Pharmacology & Therapeutics (2009); 85, 4, 402–408 doi:10.1038/clpt.2008.244
A Low Dose of Ritonavir-Boosted Atazanavir Provides Adequate Pharmacokinetic Parameters in HIV-1-Infected Thai Adults
A Avihingsanon1, J van der Lugt1,2, SJ Kerr1,3, M Gorowara1, S Chanmano1, P Ohata1, J Lange2, DA Cooper3, P Phanuphak1, DM Burger4 and K Ruxrungtham1,5
- 1HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand
- 2International Antiretroviral Therapy Evaluation Center, Amsterdam, The Netherlands
- 3National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, New South Wales, Australia
- 4Department of Clinical Pharmacology, Radboud University Nijmegen Medical Center and Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands
- 5Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Correspondence: A Avihingsanon, (Anchalee.A@hivnat.org)
Received 15 August 2008; Accepted 22 October 2008; Published online 31 December 2008.
Abstract
Several dose-finding studies of boosted protease inhibitors have demonstrated that doses lower than those recommended in Caucasian populations exhibit in the Thai population similar pharmacokinetic (PK) properties with sustained virological suppression but reduced toxicity. We therefore evaluated the PK profiles of lower than the standard doses of atazanavir/ritonavir (ATV/RTV) in 22 adult Thai patients with well-suppressed human immunodeficiency virus 1 (HIV-1) infection. The PK parameters of ATV/RTV at a dosage of 200/100 mg once daily, plus two nucleoside reverse transcriptase inhibitors, were significantly lower than those associated with a dosage of 300/100 mg once daily in the same patients. In addition, the PK parameters for the lower dosage in these Thai patients were comparable to historical data from Caucasian cohorts who received the standard dose of ATV/RTV (300/100 mg). None of the patients showed subtherapeutic values of <0.15 mg/l at any time point. Bilirubin concentration decreased significantly after dose reduction, and viral load remained at <50 copies/ml in all subjects. Therefore, ATV/RTV at a dose of 200/100 mg once daily (plus appropriate backbone medication) warrants further long-term efficacy studies, particularly in patients of Thai and other Asian ethnicities.
