Summary
Recent research indicates that physical exercise and fitness are new host factors with impact on hepatic drug metabolism, contributing to the intra- and interindividual variation in drug response.
Moderate to heavy physical exercise for a few hours reduces liver blood flow as assessed by indocyanine green clearance, leading to a decreased elimination of drugs exhibiting flow-limited metabolism (high clearance drugs) such as lignocaine (lidocainej. However, hepatic elimination of drugs exhibiting capacity-limited metabolism (low clearance drugs) such as antipyrine (phenazone), diazepam and amylobarbitone (amobarbital) is not affected by acute physical exercise.
Improved physical fitness as expressed by the maximum oxygen uptake seems to increase the elimination rate of the low clearance drug antipyrine and possibly also aminopyrine, while investigations of the biotransformation of high clearance drugs are contradictory.
The sum of research in this recent field is rather limited and the mechanism whereby changes in physical fitness influence hepatic drug metabolism needs to be established. It is not known if other liver functions are changed. If the findings also apply for drugs with a low therapeutic index, there may be a risk of exercise-induced changes in drug efficacy and toxicity.
It is suggested that future studies on host factors influencing drug metabolism should include information on physical activity.
Similar content being viewed by others
References
Alvares, A.P.; Kappas, A.; Eiseman, J.L.; Anderson, K.E.; Pantuck, C.B.; Pantuck, E.J.; Hsiao, K..-C.; Garland, W.A. and Conney, A.H.: Intraindividual variation in drug disposition. Clinical Pharmacology and Therapeutics 26: 407–419 (1979).
Anast, C.S.: Anticonvulsant drugs and calcium metabolism. New England Journal of Medicine 292: 587–588 (1975).
Balasubramaniam, K.; Mawer, G.E. and Simons, P.J.: The influence of dose on the distribution and elimination of amylobarbitone in healthy subjects. British Journal of Pharmacology 40: 578–579 (1970).
Boel, J.; Andersen, L.B.; Rasmussen, B.; Hansen, S.H. and Døssing, M.: Hepatic drug metabolism and physical fitness. Clinical Pharmacology and Therapeutics 36: 121–126 (1984).
Boyden, T.W.; Pamenter, R.W.; Stanforth, P.; Rotkis, T. and Wilmore, J.H.: Evidence for mild thyroidal impairment in women undergoing endurance training. Journal of Clinical Endocrinology and Metabolism 54: 53–56 (1982).
Connell, J.M.C.; Rapeport, W.G.; Gordon, S. and Brodie, M.J.: Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine. European Journal of Clinical Pharmacology 26: 453–456 (1984).
Ducry, J.-J.; Howald, H.; Zysset, T. and Bircher, J.: Liver function in physically trained subjects: Galactose elimination capacity, plasma disappearance of indocyanine green, and aminopyrine metabolism in long-distance runners. Digestive Disease and Sciences 24: 192–196 (1979).
Edwards, O.M.; Courtenay-Evans, R.J.; Galley, J.M.; Hunter, J. and Tait, A.D.: Changes in Cortisol metabolism following rifampicin therapy. Lancet 2: 549–551 (1974).
Few, J.D.: Effect of exercise on the secretion and metabolism of Cortisol in man. Journal of Endocrinology 62: 341–353 (1974).
Frenkl, R.; Györe, A.; Mészaros, J. and Szeberényi, Sz.: A study of the enzyme inducing effect of physical exercise in man: The “trained liver”. Journal of Sports Medicine 20: 371–376 (1980).
Frenkl, R. and Szeberényi, Sz.: Enzyme inducing effect of muscular exertion in the rat. Acta Medica Academiae Scientiarum Hungaricae 33: 95–100 (1976).
Frey, M.A.; Doerr, B.M.; Srivastava, L.S. and Glueck, C.F.: Exercise training, sex hormones, and lipoprotein relationships in men. Journal of Applied Physiology 54: 757–762 (1983).
Gikalov, I. and Bircher, J.: Dose dependence of the 14C-aminopyrine breath test: Intrasubject comparison of tracer and pharmacological doses. European Journal of Clinical Pharmacology 12: 229–233 (1977).
Gollnick, P.D. and Saltin, B.: Significance of skeletal muscle oxidative enzyyme enhancement with endurance training. Clinical Physiology 2: 1–12 (1982).
Holloszy, J.O. and Coyle, E.F.: Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. Journal of Applied Physiology 56: 831–838 (1984).
Klotz, U. and Lücke, C.: Physical exercise and disposition of diazepam. British Journal of Clinical Pharmacology 5: 349–350 (1978).
Kraus, H. and Kirsten, R.: Die Wirkung von körperlichem Training auf die mitochondriale Energieproduktion im Herzmuskel und in der Leber. Pflügers Archiv Gesamte Physiologie 320: 334–347 (1970).
LaPorte, R.E.; Adams, L.L.; Savage, D.; Brenes, G.; Dearwater, S. and Cook, T.: The spectrum of physical activity, cardiovascular disease and health: An epidemiologic perspective. American Journal of Epidemiology 120: 507–517 (1984).
Lindberg, J.S.; Fears, W.B.; Hunt, M.M.; Powell, M.R.; Boll, D. and Wade, C.E.: Exercise-induced amenorrhea and bone density. Annals of Internal Medicine 101: 647–648 (1984).
Luoma, P.V.; Sotaniemi, E.A.; Pelkonen, R.O.; Arranto, A. and Ehnholm, C.: Plasma high-density lipoproteins and hepatic microsomal enzyme induction: relation to histological changes in the liver. European Journal of Clinical Pharmacology 23: 275–282 (1982).
Meusel, H.: Developing physical fitness for the elderly through sport and exercise. British Journal of Sports Medicine 18: 4–12 (1984).
Nash, R.M.; Stein, L.; Penno, M.B.; Passananti, G.T. and Vesell, E.S.: Sources of interindividual variations in acetaminophen and antipyrine metabolism. Clinical Pharmacology and Therapeutics 36: 417–430 (1984).
Pedersen, K.E.; Madsen, J.; Kjaer, K.; Klitgaard, N.A. and Hvidt, S.: Effects of physical activity and immobilization on plasma digoxin concentration and renal digoxin clearance. Clinical Pharmacology and Therapeutics 34: 303–308 (1983).
Riester, E.F.; Pantuck, J.; Pantuck, C.B.; Passananti, G.; Vesell, E.S. and Conney, A.H.: Antipyrine metabolism during the menstrual cycle. Clinical Pharmacology and Therapeutics 28: 384–391 (1980).
Rowell, L.B.: Human cardiovascular adjustments to exercise and thermal stress. Physiological Reviews 54: 75–159 (1974).
Swartz, R.D. and Sidell, F.R.: Effects of heat and exercise on the elimination of pralidoxime in man. Clinical Pharmacology and Therapeutics 14: 83–89 (1973).
Swartz, R.D.; Sidell, F.R. and Cucinell, S.A.: Effects of physical stress on the disposition of drugs eliminated by the liver in man. Journal of Pharmacology and Experimental Therapeutics 188: 1–7 (1974).
Sweeney, G.D.: Drugs — some basic concepts..Medicine and Science in Sports and Exercise 13: 247–251 (1981).
Taylor, G. and Blaschke, T.F.: Measurement of antipyrine halflife from urinary drug concentrations. British Journal of Clinical Pharmacology 18: 650–651 (1984).
Theilade, P.; Hansen, J.M.; Skovsted, L. and Kampmann, J.P.: Effect of exercise on thyroid parameters and on metabolic clearance rate of antipyrine in man. Acta Endocrinologica 92: 271–276 (1979).
Vesell, E.S.: The antipyrine test in clinical pharmacology: Conceptions and misconceptions. Clinical Pharmacology and Therapeutics 26: 275–286 (1979).
Vesell, E.S.: Complex effects of diet on drug disposition. Clinical Pharmacology and Therapeutics 36: 285–296 (1984).
Ylitalo, P.; Hinkka, H. and Neuvonen, P.J.: Effects of exercise on the serum level and urinary excretion of tetracycline, doxycycline and sulphamethizole. European Journal of Clinical Pharmacology 12: 367–373 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Døssing, M. Effect of Acute and Chronic Exercise on Hepatic Drug Metabolism. Clin Pharmacokinet 10, 426–431 (1985). https://doi.org/10.2165/00003088-198510050-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-198510050-00004