Drug Investigation

, Volume 8, Issue 6, pp 361–368 | Cite as

Paracetamol Pharmacokinetics are Independent of Caloric Intake and Physical Activity

  • C. A. Yiamouyiannis
  • A. Harris
  • R. A. Sanders
  • B. J. Martin
  • J. B. WatkinsIII
Original Research Article


Regular physical activity provokes numerous adaptations in the gastrointestinal tract and liver. It has been suggested that these changes may alter the pharmacokinetics of drugs in humans. We addressed this suggestion by measuring paracetamol pharmacokinetics in a group of healthy young males chosen to represent the widest possible range of habitual physical activity and food intake. Daily caloric intake in the 19 men, obtained from 3-day dietary records, ranged from 1680 to 5110 kcal (21 to 66 kcal/kg). Each volunteer ingested paracetamol 1000mg in the fasted, resting state in the morning; antecubital venous blood samples were analysed for the parent compound and its glucuronide and sulfate conjugates by high-performance liquid chromatography for 6 subsequent hours. We found no evidence that paracetamol pharmacokinetics vary with physical activity or with caloric intake: (a) for the parent compound, there was no correlation in maximum blood concentrations, half-life, total clearance, or area under the curve with individual caloric intake, and (b) when volunteers were divided a priori into more active and less active groups, or a posteriori into higher and lower calorie consumers (a 70% difference in daily caloric intake), these groups had identical plasma disappearance curves for paracetamol itself and for both of its metabolites. We conclude that the enormous variation among humans in long term physical activity and food intake fails to alter any aspect of the appearance or disappearance of paracetamol from blood.


Paracetamol Caloric Intake Drug Invest Habitual Physical Activity Voluntary Exercise 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Carrió I, Estorch M, Serra-Grima R, et al. Gastric emptying in marathon runners. Gut 1989; 30: 152–5PubMedCrossRefGoogle Scholar
  2. 2.
    Yiamouyiannis CA, Martin BJ, Watkins III JB. Chronic physical activity alters hepatobiliary excretory function in rats. J Pharmacol Exp Ther 1993; 265: 321–7PubMedGoogle Scholar
  3. 3.
    Yiamouyiannis CA, Sanders RA, Watkins III JB, et al. Chronic physical activity: hepatic hypertrophy and increased total bio-transformation enzyme activity. Biochem Pharmacol 1992; 44: 121–7PubMedCrossRefGoogle Scholar
  4. 4.
    Martin BJ, Yiamouyiannis CA, Sanders RA. Exercise and hepatobiliary function. In: Siegers CP, Watkins III JB, editors. Biliary excretion of drugs and other chemicals. Stuttgart: Fischer Verlag, 1991: 497–509Google Scholar
  5. 5.
    Boel J, Anderson LB, Rasmussen B, et al. Hepatic drug metabolism and physical fitness. Clin Pharmacol Ther 1984; 36: 121–6PubMedCrossRefGoogle Scholar
  6. 6.
    Ducry J-J, Howald H, Zysset T, et al. Liver function in physically trained subjects. Dig Dis Sci 1979; 24: 192–6PubMedCrossRefGoogle Scholar
  7. 7.
    Frenkl R, Gyore A, Szeberenyi S. The effect of muscular exercise on the microsomal enzyme system of the rat liver. Eur J Appl Physiol 1980; 44: 135–40CrossRefGoogle Scholar
  8. 8.
    Watkins III JB, Crawford ST, Sanders RA. Chronic voluntary exercise may alter hepatobiliary clearance of endogenous and exogenous chemicals in rats. Drug Metab Dispos 1994; 22: 537–43PubMedGoogle Scholar
  9. 9.
    Koltz U, Maier K, Fischer C, et al. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease. N Eng J Med 1980; 303: 1499–502CrossRefGoogle Scholar
  10. 10.
    Howie D, Adriaenssens P, Prescott LF. Paracetamol metabolism following overdosage: application of high performance liquid chromatography. J Pharm Pharmacol 1977; 29: 235–7PubMedCrossRefGoogle Scholar
  11. 11.
    Albert KS, Sedman AJ, Wagner JG. Pharmacokinetics of orally administered acetaminophen in man. J Pharmacokin Biopharmaceut 1974; 2: 381–93Google Scholar
  12. 12.
    Dietz AJ, Carlson JD, Khalil SKW, et al. Effects of alcoholism on acetaminophen pharmacokinetics in man. J Clin Pharmacol 1984; 24: 205–8PubMedGoogle Scholar
  13. 13.
    Kelley MT, Walson PD, Edge JH, et al. Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clin Pharmacol Ther 1992; 52: 181–9PubMedCrossRefGoogle Scholar
  14. 14.
    Lee WH, Kramer WG, Granville GE. The effect of obesity on acetaminophen pharmacokinetics in man. J Clin Pharmacol 1981; 21: 284–7PubMedGoogle Scholar
  15. 15.
    Rumble RH, Roberts MS, Denton MJ. Effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) and its metabolites. Clin Pharmacokinet 1991; 20: 167–73PubMedCrossRefGoogle Scholar
  16. 16.
    Sahajwalla CG, Ayres JW. Multiple-dose acetaminophen pharmacokinetics. J Pharm Sci 1991; 80: 855–60PubMedCrossRefGoogle Scholar
  17. 17.
    Yamaoka K, Nakagawa T, Uno T. Application of Akaike’s Information Criterion in the evaluation of linear pharmacoki-netic equations. J Pharmacokinet Biopharm 1978; 6: 165–75PubMedGoogle Scholar
  18. 18.
    D’Argenio DZ, Schumitzky A. ADAPT II: Interactive Mathematical Software for Pharmacokinetic/Pharmacodynamic Systems Analysis. Users Guide. Biomedical Simulations Resource, University of Southern California, Los Angeles, CA, 1990Google Scholar
  19. 19.
    Gibaldi M, Perrier D. Pharmacokinetics. New York: Marcel Dekker, 1982: 1–43Google Scholar
  20. 20.
    Day WW, Weiner M. Inhibition of hepatic drug metabolism and carbon tetrachloride toxicity in Fischer-344 rats by exercise. Biochem Pharmacol 1991; 42: 181–4PubMedCrossRefGoogle Scholar
  21. 21.
    Passmore R, Durnin JGVA. Human energy expenditure. Physiol Rev 1955; 35: 801–40PubMedGoogle Scholar
  22. 22.
    Canas R, Romer JJ, Baldwin RL. Maintenance energy requirements during lactation in rats. J Nutr 1982; 112: 1879–80Google Scholar
  23. 23.
    Fausto N. Regulation of liver growth: protooncogenes and transforming growth factors. Lab Invest 1989; 60: 4–13PubMedGoogle Scholar
  24. 24.
    Mehta S, Nain CK, Yadav D, et al. Disposition of acetaminophen in children with protein calorie malnutrition. Int J Clin Pharmacol Ther Toxicol 1985; 23: 311–5PubMedGoogle Scholar
  25. 25.
    Petring OU, Adelhoj B, Ibsen M, et al. The relationship between gastric emptying of semisolids and paracetamol absorption. Br J Clin Pharmacol 1986; 22: 659–62PubMedCrossRefGoogle Scholar
  26. 26.
    deMorais SM, Chou SY, Wells PG. Biotransformation and toxicity of acetaminophen in congenic RHA rats with or without a hereditary deficiency in bilirubin UDP-glu-curonosyltransferase. Toxicol Appl Pharmacol 1992; 117: 81–7PubMedCrossRefGoogle Scholar
  27. 27.
    Gregus Z, Madhu C, Klaassen CD. Effect of microsomal enzyme inducers on biliary and urinary excretion of acetaminophen metabolites in rats. Drug Metab Dispos 1990; 18: 10–19PubMedGoogle Scholar
  28. 28.
    Villa JG, Collado PS, Almar MM, et al. Changes in the biliary excretion of organic anions following exhaustive exercise in rats. Biochem Pharmacol 1990; 40: 2519–24PubMedCrossRefGoogle Scholar
  29. 29.
    Schauer JE, Schelin A, Hanson P, et al. Dehydroepiandrosterone and a beta-agonist, energy transducers alter antioxidant enzyme systems: influence of chronic training and acute exercise in rats. Arch Biochem Biophys 1990; 283: 503–11PubMedCrossRefGoogle Scholar
  30. 30.
    Lew H, Quintanilha A. Effects of endurance training and exercise on tissue antioxidative capacity and acetaminophen detoxification. Eur J Drug Metab Pharmacokinet 1991; 16: 59–68PubMedCrossRefGoogle Scholar
  31. 31.
    Grimby G. Renal clearances during prolonged supine exercise at different loads. J Appl Physiol 1965; 20: 1294–8Google Scholar
  32. 32.
    Lee JB, Katayama S. Inflammation and non-steroidal anti-inflammatory drugs. In: Smith CM, Reynard, AM, editors. Textbook of Pharmacology. Philadelphia: Saunders, 1992: 430–2Google Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • C. A. Yiamouyiannis
    • 1
  • A. Harris
    • 1
  • R. A. Sanders
    • 1
  • B. J. Martin
    • 1
  • J. B. WatkinsIII
    • 1
  1. 1.Medical Sciences ProgramIndiana University School of MedicineBloomingtonUSA

Personalised recommendations