Clinical Pharmacokinetics

, Volume 27, Issue 2, pp 120–128

Enhancement of Drug Absorption by Antacids

An Unrecognised Drug Interaction
  • Pertti J. Neuvonen
  • Kari T. Kivistö
Review Article Pharmacokinetic Drug Interactions


Antacids are widely used for many disorders. The potential of antacids to interact with other concomitantly ingested drugs is well recognised. These interactions usually result in reduced or delayed absorption of the affected drug. However, this is not always the case.

In contrast to aluminium hydroxide, magnesium hydroxide and sodium bicarbonate can enhance the absorption of some drugs. For example, magnesium hydroxide can increase the rate and sometimes even the extent of absorption of certain nonsteroidal anti-inflammatory drugs (e.g. tolfenamic acid, mefenamic acid and ibuprofen), sulphonylurea antidiabetic agents [e.g. glipizide, glibenclamide (glyburide) and tolbutamide] and the oral anticoagulant dicoumarol (bishydroxycoumarin). These weakly acidic drugs are nonionised at gastric pH, but are sparingly water soluble. Elevation of the gastric pH by administration of magnesium hydroxide or sodium bicarbonate increases the solubility and absorption of such sparingly water soluble agents. Chelate formation may be involved in the increased absorption of dicoumarol by magnesium hydroxide. In combination antacids containing both aluminium hydroxide and magnesium hydroxide, the absorption enhancing effect of magnesium hydroxide seems to be counterbalanced by the opposing effects of aluminium hydroxide.

The clinical significance of increased drug absorption is not clear. However, accelerated and enhanced absorption of analgesic drugs may be beneficial when rapid pain relief is desired. In contrast, an unexpectedly increased hypoglycaemic or anticoagulant effect may be potentially dangerous. Therefore, a knowledge of the potential effect of antacids on the absorption of other drugs is clinically important.


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  1. 1.
    Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs. Clin Pharmacokinet 1990; 18: 210–9PubMedCrossRefGoogle Scholar
  2. 2.
    Hurwitz A. Antacid therapy and drug kinetics. Clin Pharmacokinet 1977; 2: 269–80PubMedCrossRefGoogle Scholar
  3. 3.
    Kivistö KT. Interactions in drug absorption with special reference to antacids and resins [dissertation]. Turku: Univ of Turku, 1991Google Scholar
  4. 4.
    Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976; 11: 45–54PubMedCrossRefGoogle Scholar
  5. 5.
    Nix DE, Watson WA, Lener ME, et al. Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin. Clin Pharmacol Ther 1989; 46: 700–5PubMedCrossRefGoogle Scholar
  6. 6.
    Nix DE, Wilton JH, Ronald B, et al. Inhibition of norfloxacin absorption by antacids. Antimicrob Agents Chemother 1990; 34: 432–5PubMedCrossRefGoogle Scholar
  7. 7.
    Levy G. Comparison of dissolution and absorption rates of different commercial aspirin tablets. J Pharm Sci 1961; 60: 388–92CrossRefGoogle Scholar
  8. 8.
    Leonards JR, Levy G. Reduction or prevention of aspirin-induced occult gastrointestinal blood loss in man. Clin Pharmacol Ther 1969; 10: 571–6PubMedGoogle Scholar
  9. 9.
    Mason WD, Winer N. Kinetics of aspirin, salicylic acid and salicyluric acid following oral administration of aspirin as a tablet and two buffered solutions. J Pharm Sci 1981; 70: 262–5PubMedCrossRefGoogle Scholar
  10. 10.
    Mason WD, Winer N. Influence of food on aspirin absorption from tablets and buffered solutions. J Pharm Sci 1983; 72: 819–21PubMedCrossRefGoogle Scholar
  11. 11.
    Levy G, Lampman T, Kamath BL, et al. Decreased serum salicylate concentrations in children with rheumatic fever treated with antacid. N Engl J Med 1975; 293: 323–5PubMedCrossRefGoogle Scholar
  12. 12.
    Shastri RA. Effect of antacids on salicylate kinetics. Int J Clin Pharmacol Ther Toxicol 1985; 23: 480–4PubMedGoogle Scholar
  13. 13.
    Feldman S, Carlstedt BC. Effect of antacid on absorption of enteric-coated aspirin. JAMA 1974; 227: 660–1PubMedCrossRefGoogle Scholar
  14. 14.
    Segre EJ, Sevelius H, Varady J. Effects of antacids on naproxen absorption. N Engl J Med 1974; 291: 582–3PubMedGoogle Scholar
  15. 15.
    Weber SS, Bankhurst AD, Mroszczak E, et al. Effect of Mylanta on naproxen bioavailability. Ther Drug Monit 1981; 3: 75–83PubMedGoogle Scholar
  16. 16.
    Tobert JA, DeSchepper P, Tjandramaga TB, et al. Effect of antacids on the bioavailability of diflunisal in the fasting and postprandial states. Clin Pharmacol Ther 1981; 30: 385–9PubMedCrossRefGoogle Scholar
  17. 17.
    Holmes GI, Irvin JD, Schrogie JJ. Effects of Maalox on the bioavailability of diflunisal. Clin Pharmacol Ther 1979; 25: 229Google Scholar
  18. 18.
    Neuvonen PJ, Kivistö KT. Effect of magnesium hydroxide on the absorption of tolfenamic and mefenamic acids. Eur J Clin Pharmacol 1988; 35: 495–501PubMedCrossRefGoogle Scholar
  19. 19.
    Neuvonen PJ. The effect of magnesium hydroxide on the oral absorption of Ibuprofen, ketoprofen and diclofenac. Br J Clin Pharmacol 1991; 31: 263–6PubMedCrossRefGoogle Scholar
  20. 20.
    Ojantakanen S, Hannula A-M, Marvola M. Bioavailability of Ibuprofen from hard gelatin capsules containing sodium bicarbonate, lactose or dicalcium phosphate. Acta Pharm Fenn 1990; 99: 119–26Google Scholar
  21. 21.
    Laska EM, Sunshine A, Marrero I, et al. The correlation between blood levels of Ibuprofen and clinical analgesic response. Clin Pharmacol Ther 1986; 40: 1–7PubMedCrossRefGoogle Scholar
  22. 22.
    Ambre JJ, Fischer LJ. Effect of coadministration of aluminum and magnesium hydroxides on absorption of anticoagulants in man. Clin Pharmacol Ther 1973; 14: 231–7PubMedGoogle Scholar
  23. 23.
    Bighley LD, Spivey RJ. Chelates of dicoumarol I: preparation and structure identification of magnesium chelate. J Pharm Sci 1977; 66: 1124–7PubMedCrossRefGoogle Scholar
  24. 24.
    Naggar VF, Khalil SA. In vitro antidiabetics-antacid interactions. Pharmazie 1980; 35: 412–6PubMedGoogle Scholar
  25. 25.
    Kivistö KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther 1991; 49: 39–43PubMedCrossRefGoogle Scholar
  26. 26.
    Kivistö KT, Neuvonen PJ. Differential effects of sodium bicarbonate and aluminium hydroxide on the absorption and activity of glipizide. Eur J Clin Pharmacol 1991; 40: 383–6PubMedCrossRefGoogle Scholar
  27. 27.
    Neuvonen PJ, Kivistö KT. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol 1991; 32: 215–20PubMedCrossRefGoogle Scholar
  28. 28.
    Zuccaro P, Pacifici R, Pichini S, et al. Influence of antacids on the bioavailability of glibenclamide. Drugs Exptl Clin Res 1989; 15: 165–9Google Scholar
  29. 29.
    Kivistö KT, Neuvonen PJ. Effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide. Eur J Clin Pharmacol 1992; 42: 675–80PubMedCrossRefGoogle Scholar
  30. 30.
    Tuderman V, Klinge E, Krogerus VE, et al. In vivo study of certain antacid suspensions commercially available in Finland. Acta Pharm Fenn 1979; 88: 63–72Google Scholar
  31. 31.
    Tuderman V, Klinge E, Lind H. In vitro evaluations of antacid suspensions marketed in Finland. Acta Pharm Fenn 1982; 91: 153–73Google Scholar
  32. 32.
    Bitzen P-O, Melander A, Schersten B, et al. The influence of glipizide on early insulin release and glucose disposal before and after dietary regulation in diabetic patients with different degrees of hyperglycaemia. Eur J Clin Pharmacol 1988; 35: 31–7PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Pertti J. Neuvonen
    • 1
  • Kari T. Kivistö
    • 2
  1. 1.Department of Clinical PharmacologyUniversity of HelsinkiHelsinkiFinland
  2. 2.Department of PharmacologyUniversity of TurkuTurkuFinland

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