A pharmacokinetic study of paracetamol in Thai beta-thalassemia/HbE patients.
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.
Tankanitlert
Jeeranut
J
Department of Pharmacology, Faculty of Science, Mahidol University, Rama 6 Road, Phayathai, Bangkok, 10400, Thailand. scnpm@mahidol.ac.th
Howard
Thad A
TA
Temsakulphong
Anusorn
A
Sirankapracha
Pornpan
P
Morales
Noppawan Phumala
NP
Sanvarinda
Yupin
Y
Fucharoen
Pranee
P
Ware
Russell E
RE
Fucharoen
Suthat
S
Chantharaksri
Udom
U
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*
D000082:Acetaminophen; C069744:acetaminophen cysteine; C037386:acetaminophen glucuronide; D014453:Glucuronosyltransferase; D003545:Cysteine; D001663:Bilirubin; C045667:acetaminophen sulfate ester