Tankanitlert Jeeranut, Morales Noppawan Phumala, Howard Thad A, Fucharoen Pranee, Ware Russell E, Fucharoen Suthat, Chantharaksri Udom
Department of Pharmacology, Pramongkutklao College of Medicine, Mahidol University, Bangkok, Thailand.
Pharmacology. 2007;79(2):97-103. doi: 10.1159/000097908. Epub 2006 Dec 12.
In 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 (UGT1A128) and the UGT1A6 polymorphism (UGT1A62) may affect PCM glucuronidation. To elucidate the effect of these combined polymorphisms on the PCM metabolism in thalassemic patients, 15 beta-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 UGT1A62 without UGT1A128 showed a significant, lower area under concentration-time curve (AUC(0)-->infinity) 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 UGT1A62 without UGT1A128.
