Skip to main content
Log in

Paracetamol disposition in Thai patients during and after treatment of falciparum malaria

  • Pharmacoepidemiology and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Investigations in animals have suggested that conjugation of paracetamol may be reduced in malaria. We have measured plasma concentrations and the urinary excretion of paracetamol and its phase II metabolites in eight Thai patients during uncomplicated falciparum malaria and in convalescence, following a 1000 mg single oral dose.

The apparent oral clearance (Malaria, 3.6; Convalescence, 3.9; ml·min−1·kg−1), the elimination half-life (Malaria, 3.8; Convalescence, 3.7 h) and apparent volume of distribution (Malaria, 1.2; Convalescence, 1.2; l·kg−1) of paracetamol were similar during malaria and convalescence. In addition, the urinary excretion of paracetamol and its major phase II metabolites and their formation clearances from paracetamol were not significantly different between the two study phases.

These data show that clinical malaria infection has no effect on the conjugation of paracetamol in man.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Emudianughe TS, Bickel QD, Taylor MG, Andrews B (1985) Effect of Plasmodium berghei infection on benzoic acid metabolism in mice. Experientia 41: 1407–1409

    Google Scholar 

  2. Mansor SM, Edwards G, Roberts PJ, Ward SA (1991) The effect of malaria infection on paracetamol disposition in the rat. Biochem Pharmacol 41: 1707–1711

    Google Scholar 

  3. Murdoch RT, Ghabrial H, Smallwood RA, Morgan DJ (1992) Effect of malaria on phenol conjugation pathways in perfused rat liver. Biochem Pharmacol 43: 1229–1234

    Google Scholar 

  4. Murdoch RT, Ghabrial H, Mihaly GW, Morgan DJ, Smallwood RA (1991) Malaria infection impairs glucuronidation and biliary excretion by the isolated perfused rat liver. Xenobiotica 21: 1571–1582

    Google Scholar 

  5. Ismail S, Back DJ, Edwards G (1992) The effect of malaria infection on 3′azido-3′deoxythymidine and paracetamol glucuronidation in rat liver microsomes. Biochem Pharmacol 44: 1879–1882

    Google Scholar 

  6. Ismail S, Kokwaro GO, Back DJ, Edwards G (1994) Effect of malaria infection on the pharmacokinetics of paracetamol in the rat. Xenobiotica 24: 527–533

    Google Scholar 

  7. Prescott LF (1980) Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 10: 291S-298S

    Google Scholar 

  8. Prescott LF (1969) The metabolism of phenacetin in patients with renal disease. Clin Pharmacol Ther 10: 383–394

    Google Scholar 

  9. Forfar JC, Pottage A, Toft AD, Irvine WJ, Clements JA, Prescott LF (1980) Paracetamol pharmacokinetics in thyroid disease. Eur J Clin Pharmacol 18: 269–273

    Google Scholar 

  10. Douglas AP, Savage RL, Rawlins MD (1978) Paracetamol (acetaminophen) kinetics in patients with Gilbert's syndrome. Eur J Clin Pharmacol 13: 209–212

    Google Scholar 

  11. Forrest JAH, Adriaenssens PI, Finlayson NDC, Prescott LF (1979) Paracetamol metabolism in chronic liver disease. Eur J Clin Pharmacol 15: 427–431

    Google Scholar 

  12. Trenholme GM, Williams RL, Rieckmann KH, Frischer H, Carson PE (1976) Quinine disposition during malaria and during induced fever. Clin Pharmacol Ther 19: 459–467

    Google Scholar 

  13. White NJ, Looareesuwan S, Warrell DA, Bunnag D, Harinasuta T (1982) Quinine pharmacokinetics and toxicity in cerebral and uncomplicated falciparum malaria. Am J Med 73: 564–572

    Google Scholar 

  14. Juma FD, Ogeto JO (1989) Mefloquine disposition in normals and in patients with severe Plasmodium falciparum malaria. Eur J Drug Metab Pharmacokinet 14: 15–17

    Google Scholar 

  15. Boudreau EF, Fleckenstein L, Pang MP, Childs GE, Schroeder AC, Ratnaratorn B, Phintuyothin P (1990) Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria. Clin Pharmacol Ther 48: 399–409

    Google Scholar 

  16. Edwards G, McGrath CS, Ward SA, Supanaranond W, Pukrittayakamee S, Davis TME, White NJ (1993) Interactions among primaquine, malaria infection and other antimalarials in Thai subjects. Br J Clin Pharmacol 35: 193–198

    Google Scholar 

  17. Howie D, Adriaenssens PI, Prescott LF (1977) Paracetamol metabolism following overdosage: application of HPLC. J Pharm Pharmacol 29: 235–237

    Google Scholar 

  18. Back DJ, Tjia JF (1987) Single dose primaquine has no effect on paracetamol clearance. Eur J Clin Pharmacol 32: 203–205

    Google Scholar 

  19. Looareesuwan S, White NJ, Warrell DA, Forgo I, Dubach UG, Ranalder UB, Schwartz DE (1987) Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers. Br J Clin Pharmacol 24: 37–42

    Google Scholar 

  20. Prescott LF, Yoovathaworn K, Makarananda K, Saivises R, Sriwatanakul K (1993) Impaired absorption of paracetamol in vegetarians. Br J Clin Pharmacol 36: 237–240

    Google Scholar 

  21. Critchley JAJH, Nimmo GR, Gregson CA, Woolhouse NM, Prescott LF (1986) Intersubject and ethnic differences in paracetamol metabolism. Br J Clin Pharmacol 22: 649–657

    Google Scholar 

  22. Mercado TI, Von Brand T (1954) Glycogen studies on white rats infected with Plasmodium berghei. Exp Parasitol 3: 259–266

    Google Scholar 

  23. Marsh K (1992) Malaria — a neglected disease? Parasitology 104 [Suppl]: S53-S69

    Google Scholar 

  24. White NJ (1994) Artemisinin: current status. Trans R Soc Trop Med Hyg 88 [Suppl 1]: 3–4

    Google Scholar 

  25. Rosen S, Roycroft DW, Hano JE, Barry KG (1967) The liver in malaria. Arch Pathol 83: 271–277

    Google Scholar 

  26. Fischer RG, Booth BH, Mitchell DQ, Kibbe AM (1982) Influence of trivalent influenza vaccine on serum theophylline levels. Can Med Assoc J 126: 1312–1314

    Google Scholar 

  27. Kramer P, Mc Clain CJ (1981) Depression of aminopyrine metabolism by influenza vaccination. N Engl J Med 305: 1262–1264

    Google Scholar 

  28. Scavone JM, Blyden GT, Greenblatt DJ (1989) Lack of an effect of influenza vaccine on the pharmacokinetics of of antipyrine, alprozolam, paracetamol (acetaminophen) and lorazepam. Clin Pharmacokinet 16: 180–185

    Google Scholar 

  29. Na Bangchang K, Limpaibul L, Thanavibul P, Tan-Ariya P, Karbwang J (1994) The pharmacokinetics of chloroquine in healthy Thai subjects and patients with Plasmodium vivax malaria. Br J Clin Pharmacol 38: 278–281

    Google Scholar 

  30. Wilairatana P, Looareesuwan S, Vanijanonta S, Charoenlarp P, Wittayalertpanya S (1994) Hepatic metabolism in severe falciparum malaria: caffeine clearance study. Ann Trop Med Parasitol 88: 13–20

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ismail, S., Back, D.J., Edwards, G. et al. Paracetamol disposition in Thai patients during and after treatment of falciparum malaria. Eur J Clin Pharmacol 48, 65–69 (1995). https://doi.org/10.1007/BF00202175

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00202175

Key words

Navigation