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|Title:||A pharmacokinetic study of paracetamol in Thai β-thalassemia/HbE patients|
Thad A. Howard
Noppawan Phumala Morales
Russell E. Ware
St. Jude Children's Research Hospital
The Institute of Science and Technology for Research and Development, Mahidol University
|Keywords:||Medicine;Pharmacology, Toxicology and Pharmaceutics|
|Citation:||European Journal of Clinical Pharmacology. Vol.62, No.9 (2006), 743-748|
|Abstract:||Background: Thalassemia may alter the pharmacokinetics of several drugs in thalassemic patients. Paracetamol is a commonly used analgesic and antipyretic drug which is extensively metabolized in the liver via glucuronidation. The aim of this study was to compare the pharmacokinetics of paracetamol (PCM) and its metabolites [paracetamol glucuronide (PCM-G), paracetamol sulfate (PCM-S), and paracetamol cysteine (PCM-C)] in 16 patients with 16 normal subjects. Method: Following an overnight fast, a single dose of paracetamol (1,000 mg of Tylenol®) was given and blood samples were obtained at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 7, and 9 h after dosing for determination of the plasma levels of PCM and its metabolites by high-performance liquid chromatography. Results: There was no significant difference in maximum concentration of PCM between groups. However, a significantly shorter elimination half-life of PCM was observed in the thalassemic subjects (p<0.001). Total apparent clearance of PCM was significantly faster in thalassemic subjects (p<0.01) while the apparent volume of distribution of PCM did not change. The area under the concentration time curve (AUC0->∞) of PCM-G and PCM-S increased in thalassemic subjects (p<0.05) whereas this parameter for PCM-C was slightly lower in the patients. The half-lives of PCM metabolites were significantly shorter (p<0.01) in thalassemic subjects. Conclusion: The results indicate that the elimination of PCM and its metabolites in thalassemic subjects is faster than that in normal subjects. Our pharmacokinetic data provide additional evidence that plasma PCM-G is higher in thalassemic patients with hyperbilirubinemia, which could be a casual relationship in regulating the UDP-glucuronosyltransferase expression. © Springer-Verlag 2006.|
|Appears in Collections:||Scopus 2006-2010|
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