Clinical Pharmacokinetics

, Volume 3, Issue 5, pp 337–351 | Cite as

Influence of Food on the Bioavailability of Drugs

  • Arne Melander


Food intake exerts a complex influence on the bioavailability of drugs. It may interfere not only with tablet disintegration, drug dissolution and drug transit through the gastrointestinal tract, but may also affect the metabolic transformation of drugs in the gastrointestinal wall and in the liver. Different food components can have different effects, and food may interact in opposite ways, even with drugs that are chemically related. Therefore, the net effect of food on drug bioavailability can be predicted only by direct clinical studies of the drug in question.

As judged mainly from single meal, single dose studies, food intake enhances the bioavailability of several different drugs, such as propranolol, metoprolol, hydrallazine, hydrochlorothiazide, canrenone (from spironolactone), nitrofurantoin, erythromycin (stearate), dicoumarol, phenytoin and carbamazepine, but reduces that of drugs such as isoniazid, rifampicin, tetracycline, penicillin and ampicillin, while having no consistent effect on the bioavailability of metronidazole, oxazepam, melperone, propylthiouracil, sulphasomidine and sulphonylureas. For some drugs such as digoxin and paracetamol, the rate but not the extent of absorption is reduced.

Food may enhance bioavailability even though, or rather because, the rate of gastric emptying is reduced; this is apparently the case with hydrochlorolhiazide and nitrofurantoin. The food induced enhancement of bioavailability of propranolol, metoprolol and hydrallazine is probably due to reduced first pass metabolism of these drugs, while food induced improvement of drug dissolution may explain the enhanced bioavailability of carbamazepine, canrenone, dicoumarol and phenytoin. An increased gastrointestinal pH may be in part the cause of the food induced reduction of the bioavailability of drugs such as isoniazid and tetracycline.

In addition to single meal effects, repeated intake of protein-rich meals enhance, while carbohydrate-rich meals reduce, the rate of oxidation of antipyrine and theophylline. Moreover, intake of charcoal broiled meat markedly accelerates the oxidation of phenacetin and variably accelerates elimination of theophylline. Thus, food and its components and contaminants may have both short and long term effects on both the absorptive and biotransformation processes influencing systemic availability of drugs.


Theophylline Clinical Pharmacology Gastric Emptying Metoprolol Isoniazid 
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  1. Acocella, G.: Clinical pharmacokinetics of rifampicin. Clinical Pharmacokinetics 3: 128–143 (1978).CrossRefGoogle Scholar
  2. Barr, W.H.; Adir, J. and Garrettson, L.: Decrease of tetracycline absorption in man by sodium bicarbonate. Clinical Pharmacology and Therapeutics 12: 779–784 (1971).PubMedGoogle Scholar
  3. Bates, T.R.; Sequeira, J.A. and Tembo, A.V.: Effect of food on nitrofurantoin absorption. Clinical Pharmacology and Therapeutics 16: 63–68 (1974).PubMedGoogle Scholar
  4. Bauer, G.; Rieckmann, P. and Schaumann, W.: Einfluss von Teilchengrosse und Losungsvermittlern auf die Resorption von Spironolacton aus dem Magen-Darmtrakt. Arzneimittel-Forschung 12: 487–489 (1962).PubMedGoogle Scholar
  5. Beermann, B. and Groschinsky-Grind, M.: Gastrointestinal absorption of hydrochlorothiazide enhanced by concomitant intake of food. European Journal of Clinical Pharmacology. In press (1978a).Google Scholar
  6. Beermann, B. and Groschinsky-Grind. M.: Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline. European Journal of Clinical Pharmacology. In press (1978b).Google Scholar
  7. Binns, T.B.: Absorption and Distribution of Drugs (Livingstone. London 1964).Google Scholar
  8. Bogentoft, C.; Carlsson. I.: Ekenved, G. and Magnusson, A.: Influence of food on the absorption of acetylsalicylic acid from enteric-coated dosage forms. European Journal of Clinical Pharmacology. In press (1978).Google Scholar
  9. Chasseaud, L.F. and Taylor, T.: Bioavailability of drugs from formulations after oral administration. Annual Review of Pharmacology 14: 35–46 (1974).CrossRefGoogle Scholar
  10. Conney, A.H.; Pantuck, E.J.; Hsiao, K.-C.; Carland, W.A.; Anderson, K.E.; Alvares, A.P. and Kappas, A.: Enhanced phenacetin metabolism in human subjects fed charcoal-broiled beef. Clinical Pharmacology and Therapeutics 20: 633–642 (1976).PubMedGoogle Scholar
  11. Crounse, R.G.: Effective use of griseofulvin. Archives of Dermatology 87: 176–180 (1963).PubMedCrossRefGoogle Scholar
  12. Curry, S.H.; D’mello, A. and Mould, G.P.: Destruction of chlorpromazine during absorption in the rat in vivo and in vitro. British Journal of Pharmacology 42: 403–411 (1971).PubMedCrossRefGoogle Scholar
  13. Dahl, S.G. and Strandjord, R.E.: Pharmacokinetics of chlorpromazine after single and chronic dosage. Clinical Pharmacology and Therapeutics 21: 437–448 (1977).PubMedGoogle Scholar
  14. Doluisio, J.T.; La Piana, J.C.; Vilkinson, G.R. and Dittert, L.W.: Pharmacokinetic interpretation of dicloxacillin levels in serum after extravascular administration. Antimicrobial Agents and Chemotherapy 9: 49–55 (1969).PubMedGoogle Scholar
  15. Editorial: Food and the handling of drugs. British Medical Journal 1: 1304 (1977).CrossRefGoogle Scholar
  16. Ervik, M.: Quantitative determination of metoprolol in plasma and urine by gas chromatography. Acta Pharmacologica et Toxicologica 36 (Suppl. 5): 136–144 (1975).PubMedGoogle Scholar
  17. Fiegler, D.I.; Dryant, M.; Burley, D.M.; Citron, K.M. and Standen, S.M.: Effect of meals on rifampicin absorption. Lancet 2: 197–198 (1974).CrossRefGoogle Scholar
  18. Greenblatt, D.J.; Duhme, D.W.; Koch-Weser, J. and Smith, T.W.: Bioavailability of digoxin tablets and elixir in the fasting and postprandial states. Clinical Pharmacology and Therapeutics 16: 444–449 (1974).PubMedGoogle Scholar
  19. Heading, R.C.; Nimmo, J.; Prescott, L.F. and Tothill, P.: The dependence of paracetamol absorption on the rate of gastric emptying. British Journal of Pharmacology 47: 415–421 (1973).PubMedCrossRefGoogle Scholar
  20. Hirsch, H.H. and Finland, M.: Effect of food on the absorption of erythromycin Propionate, erythromycin stearate and triacetyloleandomycin. American Journal of Medical Science 237: 693–699 (1959).CrossRefGoogle Scholar
  21. Hurwitz, A.: Antacid therapy and drug kinetics. Clinical Pharmacokinetics 2: 269–280 (1977).PubMedCrossRefGoogle Scholar
  22. Hurwitz, A. and Schlozman, D.L.: Effects of antacids on gastrointestinal absorption of isoniazid in rat and man. American Review of Respiratory Diseases 109: 41–44 (1974).Google Scholar
  23. Jaffe, J.M.: Effect of propantheline on nitrofurantoin absorption. Journal of Pharmaceutical Sciences 64: 1725 (1975).Google Scholar
  24. Jaffe, J.M.; Coliazzi, J.L. and Barry, H.: Effects of dietary components on gastrointestinal absorption of acetaminophen tablets in man. Journal of Pharmaceutical Sciences 60: 1646–1650 (1971).PubMedCrossRefGoogle Scholar
  25. Jenne, J.W.; Partial purification and properties of the isoniazid transacetylase in human liver. Its relationship to the acetylation of p-aminosalicylic acid. Journal of Clinical Investigation 44: 1992–2001 (1965).CrossRefGoogle Scholar
  26. Johansson, O.; Lindberg, T. and Melander, A.: On the mechanism of Phenytoin absorption from rat small intestine. European Journal of Clinical Investigation. Submitted for publication (1978).Google Scholar
  27. Johnson, B.F.; O’Grady, J.; Sabey, G.A. and Bye, C.: Effect of a standard breakfast on digoxin absorption in normal subjects. Clinical Pharmacology and Therapeutics 23: 315–319 (1978).PubMedGoogle Scholar
  28. Jordan, M.C.; de Maine, J. and Kirby, W.: Clinical pharmacology of pivampicillin as compared with ampicillin. Antimicrobial Agents and Chemotherapy 2: 438–441 (1970).Google Scholar
  29. Kamme, C.; Kahlmeter, G. and Melander, A.: Evaluation of spiramycin as a therapeutic agent for elimination of nasopharyngeal pathogens. Possible use of spiramycin for middle ear infections and for gonococcal and meningococcal nasopharyngeal carriage. Scandinavian Journal of Infectious Diseases. In press (1978).Google Scholar
  30. Kappas, A.; Anderson, K.E.; Conney, A.H. and Alvares, A.P.: Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. Clinical Pharmacology and Therapeutics 20: 643–653 (1976).PubMedGoogle Scholar
  31. Kappas, A.; Alvares, A.P.; Anderson, K.E.; Pantuck, E.J.; Pantuck, C.B.; Chang, R. and Conney, A.H.: Effect of charcoalbroiled beef on antipyrine and theophylline metabolism. Clinical Pharmacology and Therapeutics 23: 445–450 (1978).PubMedGoogle Scholar
  32. Katchen, B.: Correlation of dissolution rate and drug absorption in man. Acta Pharmacologica et Toxicologica 29 (Suppl. 3): 88–95 (1971).PubMedGoogle Scholar
  33. Kirby, W.M.M.; Roberts, C.E. and Burdick, R.E.: Comparison of two new tetracyclines with tetracycline and demethylchlortetracycline. Antimicrobial Agents and Chemotherapy 1: 286–292 (1961).Google Scholar
  34. Klein, J.O. and Finland, M.: Medical progress: The new penicillins. New England Journal of Medicine 269: 1019–1024 (1963).PubMedCrossRefGoogle Scholar
  35. Koch-Weser, J.: Bioavailability of drugs. New England Journal of Medicine 291: 233–237. 503–506 (1974).PubMedCrossRefGoogle Scholar
  36. Lesser, J.M.; Israili, Z.H.; Davis, D.C. and Dayron, P.G.; Metabolism and disposition of hydralazine-14C in man and dog. Drug Metabolism and Disposition 2: 351–360 (1974).PubMedGoogle Scholar
  37. Levine, R.R.: Factors affecting gastro-intestinal absorption of drugs. American Journal of Digestive Diseases 15: 171–180 (1970).PubMedCrossRefGoogle Scholar
  38. Levy, R.H.; Pitlick, W.H.; Troupin, A.S.; Green, J.R. and Neal, J.M.: Pharmacokinetics of carbamazepine in normal man. Clinical Pharmacology and Therapeutics 17: 657–668 (1975).PubMedGoogle Scholar
  39. Linnoila, M.; Korttila, K. and Mattila, M.J.; Effect of food and repeated injections on serum diazepam levels. Acta Pharmacologica et Toxicologica 36: 181–186 (1975).PubMedCrossRefGoogle Scholar
  40. Macdonald, H.; Place, V.A.; Falk, H. and Darken, M.A.: Effect of food on absorption of Sulfonamides in man. Chemotherapia 12: 282–285 (1967).CrossRefGoogle Scholar
  41. McGilveray, I.J. and Mattok, G.L.: Some factors affecting the absorption of paracetamol. Journal of Pharmacy and Pharmacology 24: 615–619 (1972).PubMedCrossRefGoogle Scholar
  42. Mattok, G.L. and McGilveray, I.J.: The effect of food intake and sleep on the absorption of acetaminophen. Revue Canadienne de Biologie 32: 77–84 (1973).PubMedGoogle Scholar
  43. Malmborg, A.-S.: Absorption of erythromycin stearate after oral administration. Current Medical Research and Opinion 5 (Suppl. 2): 15–18 (1978).CrossRefGoogle Scholar
  44. Melander, A.: Enhancement of hydralazine bioavailability by concomitant intake of food; in Pharmacological and clinical aspects of hydralazine (Apresoline) in today’s treatment of hypertension. Symposium. Oslo. 1977; Hassle-Ciba-Geigy A/S. Strammen. Norway, In press (1978).Google Scholar
  45. Melander, A.; Brante, G.; Johansson, O.; Lindberg, T. and Wahlin, E.; Influence of food intake on the absorption of Phenytoin in man. European Journal of Clinical investigation. Submitted for publication (1978a).Google Scholar
  46. Melander, A.; Haglund, G.: Larsson, H. and Molander, L.: Singledose kinetics of melperone: influence of food intake and of age. Manuscript in preparation (1978b).Google Scholar
  47. Melander, A.; Berlin-Wahlen, A.; Bodin, N.-O.; Danielson, K.; Gustafsson, B.; Lindgren, S. and Westerlund, D.: Bioavailability of D-propoxyphene, acetyl salicylic acid, and Phenazone in a combination tablet (Doleron): interindividual variation and influence of food intake. Acta Medica Scaridinavica 202: 119–124 (1977f).CrossRefGoogle Scholar
  48. Melander, A.; Danielson, K.; Hanson, A.; Jansson, L.; Rerup, C.; Schersten, B.; Thulin, T. and Wahlin, E.: Reduction of isoniazid bioavailability in normal men by concomitant intake of food. Acta Medica Scandinavica 200: 93–97 (1976a).PubMedCrossRefGoogle Scholar
  49. Melander, A.; Wahlin, E.; Danielson, K. and Rerup, C.: On the influence of concomitant food intake on Sulfonamide bioavailability. Acta Medica Scandinavica 200: 497–500 (1976b).PubMedCrossRefGoogle Scholar
  50. Melander, A.; Danielson, K.; Hanson, A.; Rudell, B.; Schersten, B.; Thulin, T. and Wahlin, E.: Enhancement of hydralazine bioavailability by food. Clinical Pharmacology and Therapeutics 22: 104–107 (1977a).PubMedGoogle Scholar
  51. Melander, A.; Danielson, K.; Schersten, B.; Thulin, T. and Wahlin, E.: Enhancement by food of canrenone bioavailability from Spironolactone. Clinical Pharmacology and Therapeutics 22: 100–103 (1977b).PubMedGoogle Scholar
  52. Melander, A.; Danielson, K.; Schersten, B. and Wahlin, E.: Enhancement of the bioavailability of Propranolol and metoprolol by food. Clinical Pharmacology and Therapeutics 22: 108–112 (1977c).PubMedGoogle Scholar
  53. Melander, A.; Danielson, K.; Vessman, J. and Wahlin, E.: Bioavailability of oxazepam: absence of influence of food intake. Acta Pharmacologica et Toxicologica 40: 584–588 (1977e).PubMedGoogle Scholar
  54. Melander, A.; Kahlmeter, G.; Kamme, C. and Ursing, B.: Bioavailability of metronidazole in fasting and non-fasting healthy subjects and in patients with Crohn’s disease. European Journal of Clinical Pharmacology 12: 69–72 (1977d).PubMedCrossRefGoogle Scholar
  55. Melander, A. and Wahlin, E.: Enhancement of dicumarol bioavailability by concomitant food intake. European Journal of Clinical Pharmacology. Submitted for publication (1978).Google Scholar
  56. Melander, A.; Wahlin, E.; Danielson, K. and Hanson, A.: Bioavailability of Propylthiouracil: interindividual variation and influence of food intake. Acta Medica Scandinavica 201: 41–44 (1977g).PubMedCrossRefGoogle Scholar
  57. Mitchison, D.A.: Plasma concentrations of isoniazid in the treatment of tuberculosis; in Davies and Pritchard (Eds) Biological effects of drugs in relation to their plasma concentrations, p.169–182 (Macmillan. London 1973).Google Scholar
  58. Neu, H.C. Antimicrobial activity and human pharmacology of amoxycillin. Journal of Infectious Diseases 129 (Suppl.) 123 (June 1974).CrossRefGoogle Scholar
  59. Neuvonen, P.J.: Interactions with the absorption of tetracyclines. Drugs 11: 45–54 (1976).PubMedCrossRefGoogle Scholar
  60. Neuvonen, P.J. and Turakka, H.: Inhibitory effect of various iron salts on the absorption of tetracycline in man. European Journal of Clinical Pharmacology 7: 357–360 (1974).PubMedCrossRefGoogle Scholar
  61. Pierpaoli, P.G.: Drug therapy and diet. Drug Intelligence and Clinical Pharmacy 6: 89–99 (1972).Google Scholar
  62. Prescott, L.F.: Gastrointestinal absorption of drugs. Medical Clinics of North America 58: 907–916 (1974).PubMedGoogle Scholar
  63. Roholt, K.; Nielsen, B. and Kristensen, E.: Clinical pharmacology of pivampicillin. Antimicrobial Agents and Chemotherapy 6: 563–571 (1974).PubMedCrossRefGoogle Scholar
  64. Rosenberg, H.A. and Bates, T.R.: The influence of food on nitrofurantoin bioavailability. Clinical Pharmacology and Therapeutics 20: 227–232 (1976).PubMedGoogle Scholar
  65. Sanchez, N.; Sheiner, L.B.. Halkin, H. and Melmon, K.L.: Pharmacokinetics of digoxin: interpreting bioavailability. British Medical Journal 4: 132–136 (1973).PubMedCrossRefGoogle Scholar
  66. Sartor, G.; Melander, A.; Schersten, B. and Wahlin, E.: Influence of food intake on the kinetics and effects of sulfonylurea drugs in healthy subjects and in diabetic patients; in Selected Topics in Diabetes. Proceedings of an International Meeting, Tirrenia, Italy, 1977 pp.129–139 (Carlo Erba, Milan 1978a).Google Scholar
  67. Sartor, G.; Schersten, B. and Melander, A.: Effects of glipizide and food intake on the blood levels of glucose and insulin in diabetic patients. Acta Medica Scandinavica 203: 211–214 (1978b).PubMedCrossRefGoogle Scholar
  68. Shand, D.G.: Pharmacokinetic properties of the beta-adrenergic receptor blocking drugs. Drug 7: 39–47 (1974).CrossRefGoogle Scholar
  69. Smith, R.B.; Dittert, L.W.; Griffen, Jr. W.O. and Doluisio,. J.T.: Pharmacokinetics of pentobarbital after intravenous and oral administration. Journal of Pharmacokinetics and Biopharmaceutics 1: 5–15 (1973).Google Scholar
  70. Sutter, J.L. and Lan, E.P.K.: Spironolactone: in Florey, K. (Ed) Analytical Profiles of Drug Substances, vol. 4, p.411 (Academic Press. New York 1975).Google Scholar
  71. Ther, L. and Winne, D.: Drug absorption. Annual Review of Pharmacology 11: 57–70 (1971).PubMedCrossRefGoogle Scholar
  72. Wagner, J.G.: Drug bioavailability studies. Hosnital Practice 12: 119–127 (1977).Google Scholar
  73. Welling, P.G.: How food and fluid affect drug absorption. Postgraduate Medicine 62: 73–82 (1977).PubMedGoogle Scholar
  74. Welling, P.G.; Lyons, L.L.; Craig, W.A. and Trochia, B.S.: Influence of diet and fluid on bioavailability of theophylline. Clinical Pharmacology and Therapeutics 17: 475–480 (1975).PubMedGoogle Scholar
  75. White, R.J.; Chamberlain, D.S.; Howard, M. and Smith, T.W.: Plasma concentrations of digoxin after oral administration in the fasting and postprandial state. British Medical Journal 1: 380–381 (1971).PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press 1978

Authors and Affiliations

  • Arne Melander
    • 1
    • 2
  1. 1.Department of Clinical PharmacologyUniversity of Lund, Malmo General HospitalMalmoSweden
  2. 2.Department of Community Care SciencesDalbyAustralia

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