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A pharmacokinetic study of paracetamol in Thai β-thalassemia/HbE patients

  • Pharmacokinetics and Disposition
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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.

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Acknowledgements

This work was supported by Thailand Research Fund and National Center for Genetic Engineering and Biotechnology. Jeeranut Tankanitlert was a recipient of the scholarship from the Ministry of University Affairs. Prof. Suthat Fucharoen is a senior scholar of Thailand Research Fund. The authors thank Dr. T.W. Flegel for carefully checking the manuscript.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Science, Mahidol University, Rama 6 Road, Phayathai, Bangkok, 10400, Thailand

    Jeeranut Tankanitlert, Anusorn Temsakulphong, Noppawan Phumala Morales, Yupin Sanvarinda & Udom Chantharaksri

  2. Division of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, 38105, US

    Thad A. Howard & Russell E. Ware

  3. Thalassemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Bangkok, 10400, Thailand

    Pornpan Sirankapracha, Pranee Fucharoen & Suthat Fucharoen

Authors
  1. Jeeranut Tankanitlert
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  2. Thad A. Howard
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  3. Anusorn Temsakulphong
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  4. Pornpan Sirankapracha
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  7. Pranee Fucharoen
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  8. Russell E. Ware
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  9. Suthat Fucharoen
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  10. Udom Chantharaksri
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Correspondence to Jeeranut Tankanitlert.

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Tankanitlert, J., Howard, T.A., Temsakulphong, A. et al. A pharmacokinetic study of paracetamol in Thai β-thalassemia/HbE patients. Eur J Clin Pharmacol 62, 743–748 (2006). https://doi.org/10.1007/s00228-006-0167-2

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  • DOI: https://doi.org/10.1007/s00228-006-0167-2

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