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|Title:||Effects of combined UDP-glucuronosyltransferase (UGT) 1A1*28 and 1A6*2 on paracetamol pharmacokinetics in β-thalassemia/HbE|
Noppawan Phumala Morales
Thad A. Howard
Russell E. Ware
Phramongkutklao College of Medicine
The Institute of Science and Technology for Research and Development, Mahidol University
St. Jude Children's Research Hospital
|Keywords:||Pharmacology, Toxicology and Pharmaceutics|
|Citation:||Pharmacology. Vol.79, No.2 (2007), 97-103|
|Abstract:||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 (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.|
|Appears in Collections:||Scopus 2006-2010|
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