Noppaket Singkham1,2, Anchalee Avihingsanon3,4, Narukjaporn Thammajaruk3, Kiat Ruxrungtham3,4, Torsak Bunupuradah3, Sasisopin Kiertiburanakul5, Ploenchan Chetchotisakd6, David M Burger7, Sean Emery8, Baralee Punyawudho1,9. 1. Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. 2. PhD's Degree Program in Pharmacy, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. 3. HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 4. Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 5. Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 6. Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 7. Department of Pharmacy, Radbound University Medical Center, Nijmegen, The Netherlands. 8. Faculty of Medicine, University of New South Wales, Sydney, Australia. 9. Pharmacoepidemiology & Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Abstract
Aim: To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). Patients & methods: The concentration-to-dose ratios were compared between different genotype groups of CYP3A5, ABCB1, SLCO1B1 and NR1I2 in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Results: Higher concentrations of ATV and RTV were significantly associated with CYP3A5 6986 GG and SLCO1B1 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Conclusion: Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.
Aim: To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). Patients & methods: The concentration-to-dose ratios were compared between different genotype groups of CYP3A5, ABCB1, SLCO1B1 and NR1I2 in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Results: Higher concentrations of ATV and RTV were significantly associated with CYP3A5 6986 GG and SLCO1B1 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Conclusion: Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.