Jeeranut TankanitlertNoppawan Phumala MoralesThad A. HowardPranee FucharoenRussell E. WareSuthat FucharoenUdom ChantharaksriPhramongkutklao College of MedicineMahidol UniversityThe Institute of Science and Technology for Research and Development, Mahidol UniversitySt. Jude Children's Research Hospital2018-08-242018-08-242007-04-01Pharmacology. Vol.79, No.2 (2007), 97-103003170122-s2.0-34147164572https://repository.li.mahidol.ac.th/handle/123456789/25108In addition to pathophysiological changes, genetic variations can alter drug pharmacokinetics in patients with thalassemia. Numerous drugs are metabolized by UDP-glucuronosyltransferases (UGT) including paracetamol (PCM), a widely used analgesic. Co-occurrence of the UGT1A1 polymorphism (UGT1A1*28) and the UGT1A6 polymorphism (UGT1A6*2) may affect PCM glucuronidation. To elucidate the effect of these combined polymorphisms on the PCM metabolism in thalassemic patients, 15 β-thalassemia/hemoglobin E subjects with three different UGT1A genotypes received a single oral dose of 1,000 mg PCM. Drug disposition was determined by HPLC. Patients who have UGT1A6*2 without UGT1A1*28 showed a significant, lower area under concentration-time curve (AUC0→∞) of PCM, PCM-glucuronide and PCM-sulfate than those of the patients with wild-type UGT1A1 and UGT1A6 (p < 0.05). In addition, a high elimination rate constant and clearance of PCM and its metabolites were also found in these patients (p < 0.05). Ourstudy suggests that a subtherapeutic level of PCM may occur in patients who have UGT1A6*2 without UGT1A1*28. Copyright © 2007 S. Karger AG.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1159/000097908