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Influence of Food on the Bioavailability of Drugs

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Abstract

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.

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References

  • Acocella, G.: Clinical pharmacokinetics of rifampicin. Clinical Pharmacokinetics 3: 128–143 (1978).

    Article  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Bates, T.R.; Sequeira, J.A. and Tembo, A.V.: Effect of food on nitrofurantoin absorption. Clinical Pharmacology and Therapeutics 16: 63–68 (1974).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Beermann, B. and Groschinsky-Grind, M.: Gastrointestinal absorption of hydrochlorothiazide enhanced by concomitant intake of food. European Journal of Clinical Pharmacology. In press (1978a).

  • Beermann, B. and Groschinsky-Grind. M.: Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline. European Journal of Clinical Pharmacology. In press (1978b).

  • Binns, T.B.: Absorption and Distribution of Drugs (Livingstone. London 1964).

    Google Scholar 

  • 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).

  • Chasseaud, L.F. and Taylor, T.: Bioavailability of drugs from formulations after oral administration. Annual Review of Pharmacology 14: 35–46 (1974).

    Article  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Crounse, R.G.: Effective use of griseofulvin. Archives of Dermatology 87: 176–180 (1963).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Dahl, S.G. and Strandjord, R.E.: Pharmacokinetics of chlorpromazine after single and chronic dosage. Clinical Pharmacology and Therapeutics 21: 437–448 (1977).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Editorial: Food and the handling of drugs. British Medical Journal 1: 1304 (1977).

    Article  Google Scholar 

  • Ervik, M.: Quantitative determination of metoprolol in plasma and urine by gas chromatography. Acta Pharmacologica et Toxicologica 36 (Suppl. 5): 136–144 (1975).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • Hurwitz, A.: Antacid therapy and drug kinetics. Clinical Pharmacokinetics 2: 269–280 (1977).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • Jaffe, J.M.: Effect of propantheline on nitrofurantoin absorption. Journal of Pharmaceutical Sciences 64: 1725 (1975).

    Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • 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).

  • 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).

    PubMed  CAS  Google Scholar 

  • 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 

  • 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).

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Katchen, B.: Correlation of dissolution rate and drug absorption in man. Acta Pharmacologica et Toxicologica 29 (Suppl. 3): 88–95 (1971).

    PubMed  CAS  Google Scholar 

  • 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 

  • Klein, J.O. and Finland, M.: Medical progress: The new penicillins. New England Journal of Medicine 269: 1019–1024 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Koch-Weser, J.: Bioavailability of drugs. New England Journal of Medicine 291: 233–237. 503–506 (1974).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Levine, R.R.: Factors affecting gastro-intestinal absorption of drugs. American Journal of Digestive Diseases 15: 171–180 (1970).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  CAS  Google Scholar 

  • McGilveray, I.J. and Mattok, G.L.: Some factors affecting the absorption of paracetamol. Journal of Pharmacy and Pharmacology 24: 615–619 (1972).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • Malmborg, A.-S.: Absorption of erythromycin stearate after oral administration. Current Medical Research and Opinion 5 (Suppl. 2): 15–18 (1978).

    Article  CAS  Google Scholar 

  • 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).

  • 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).

  • Melander, A.; Haglund, G.: Larsson, H. and Molander, L.: Singledose kinetics of melperone: influence of food intake and of age. Manuscript in preparation (1978b).

  • 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).

    Article  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Melander, A. and Wahlin, E.: Enhancement of dicumarol bioavailability by concomitant food intake. European Journal of Clinical Pharmacology. Submitted for publication (1978).

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Neu, H.C. Antimicrobial activity and human pharmacology of amoxycillin. Journal of Infectious Diseases 129 (Suppl.) 123 (June 1974).

    Article  Google Scholar 

  • Neuvonen, P.J.: Interactions with the absorption of tetracyclines. Drugs 11: 45–54 (1976).

    Article  PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Pierpaoli, P.G.: Drug therapy and diet. Drug Intelligence and Clinical Pharmacy 6: 89–99 (1972).

    Google Scholar 

  • Prescott, L.F.: Gastrointestinal absorption of drugs. Medical Clinics of North America 58: 907–916 (1974).

    PubMed  CAS  Google Scholar 

  • Roholt, K.; Nielsen, B. and Kristensen, E.: Clinical pharmacology of pivampicillin. Antimicrobial Agents and Chemotherapy 6: 563–571 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg, H.A. and Bates, T.R.: The influence of food on nitrofurantoin bioavailability. Clinical Pharmacology and Therapeutics 20: 227–232 (1976).

    PubMed  CAS  Google Scholar 

  • Sanchez, N.; Sheiner, L.B.. Halkin, H. and Melmon, K.L.: Pharmacokinetics of digoxin: interpreting bioavailability. British Medical Journal 4: 132–136 (1973).

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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).

    Article  PubMed  CAS  Google Scholar 

  • Shand, D.G.: Pharmacokinetic properties of the beta-adrenergic receptor blocking drugs. Drug 7: 39–47 (1974).

    Article  CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • 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 

  • Ther, L. and Winne, D.: Drug absorption. Annual Review of Pharmacology 11: 57–70 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Wagner, J.G.: Drug bioavailability studies. Hosnital Practice 12: 119–127 (1977).

    CAS  Google Scholar 

  • Welling, P.G.: How food and fluid affect drug absorption. Postgraduate Medicine 62: 73–82 (1977).

    PubMed  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Clinical Pharmacology, University of Lund, Malmo General Hospital, Entr 73, Plane 4, Room 407, S-214 01, Malmo, Sweden

    Arne Melander

  2. Department of Community Care Sciences, Dalby, Australia

    Arne Melander

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Melander, A. Influence of Food on the Bioavailability of Drugs. Clin Pharmacokinet 3, 337–351 (1978). https://doi.org/10.2165/00003088-197803050-00001

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