title: A pharmacokinetic study of paracetamol in Thai beta-thalassemia/HbE patients.
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.
  
  
  METHODS
  Following an overnight fast, a single dose of paracetamol (1,000 mg of Tylenol(R)) 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 (AUC(0->infinity)) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Rama 6 Road, Phayathai, Bangkok, 10400, Thailand. scnpm@mahidol.ac.th
authors.forename: Jeeranut
authors.initials: J
authors.lastname: Tankanitlert
authors.forename: Thad A
authors.initials: TA
authors.lastname: Howard
authors.forename: Anusorn
authors.initials: A
authors.lastname: Temsakulphong
authors.forename: Pornpan
authors.initials: P
authors.lastname: Sirankapracha
authors.forename: Noppawan Phumala
authors.initials: NP
authors.lastname: Morales
authors.forename: Yupin
authors.initials: Y
authors.lastname: Sanvarinda
authors.forename: Pranee
authors.initials: P
authors.lastname: Fucharoen
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Udom
authors.initials: U
authors.lastname: Chantharaksri
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001663:Bilirubin / Q000097:blood; D003545:Cysteine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D014453:Glucuronosyltransferase / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017086:beta-Thalassemia / Q000378:metabolism*
chemical_list: D000082:Acetaminophen; C069744:acetaminophen cysteine; C037386:acetaminophen glucuronide; D014453:Glucuronosyltransferase; D003545:Cysteine; D001663:Bilirubin; C045667:acetaminophen sulfate ester