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Effect of Calcium and Antacids on Phenytoin Bioavailability

William R. Garnett, PharmD; Barry L. Carter; John M. Pellock, MD
Arch Neurol. 1980;37(7):467-467. doi:10.1001/archneur.1980.00500560097022
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To the Editor.—  We read with interest the article by Chapron et al entitled "Effect of Calcium and Antacids on Phenytoin Bioavailability" (36:436-438, 1979) because we have just completed a similar experiment with different results.We used more subjects, equal neutralizing capacities of antacids rather than equal volumes,1 a different dose of phenytoin, and gave the antacids in the recommended dosage schedule for peptic ulcer.2Each of eight subjects served as his own control. We randomly assigned the subjects to receive 600 mg of phenytoin alone or with 160 mEq of aluminum hydroxide-magnesium hydroxide gel, calcium carbonate, or aluminum hydroxide-magnesium trisilicate, administered one and three hours after meals and at bedtime. Each subject received phenytoin alone twice and phenytoin plus each of the antacids. Samples were analyzed by the EMIT system,3.4 and absorption was determined by using the trapezoidal rule to calculate area under the curve (AUC).

REFERENCES

Fordtran JS, Morawski SG, Richardson CT:  In vivo and in vitro evaluation of liquid antacids . N Engl J Med 288:923-928, 1973;.
Peterson WL, Sturdevant RAL, Frank HD, et al:  Healing of duodenal ulcer with an antacid regimen . N Engl J Med 297:341-345, 1977;.
Spiehler V:  Radio immunoassay enzyme immunoassay, spectrophotometry, and gas-liquid chromatography compared for determination of phenobarbital and diphenylhydantoin . Clin Chem 22:749-753, 1976;.
Legaz M, Vidmantas RA:  Correlation of the 'EMIT' antiepileptic drug assay with a gas liquid chromatographic method . Clin Biochem 9:35-38, 1976;.
Gibaldi M, Perrier D: Pharmacokinetics . New York, Marcel Dekker Inc, 1975;, pp 293-296.
Snedecor GW:  Comparisons factorial arrangements of treatments , in Statistical Methods , ed 5. Ames, Iowa State College Press, 1956;, pp 329-333.
Kutt H:  Interaction of antiepileptic drugs . Epilepsia 16:393-402, 1975;.

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Fordtran JS, Morawski SG, Richardson CT:  In vivo and in vitro evaluation of liquid antacids . N Engl J Med 288:923-928, 1973;.
Peterson WL, Sturdevant RAL, Frank HD, et al:  Healing of duodenal ulcer with an antacid regimen . N Engl J Med 297:341-345, 1977;.
Spiehler V:  Radio immunoassay enzyme immunoassay, spectrophotometry, and gas-liquid chromatography compared for determination of phenobarbital and diphenylhydantoin . Clin Chem 22:749-753, 1976;.
Legaz M, Vidmantas RA:  Correlation of the 'EMIT' antiepileptic drug assay with a gas liquid chromatographic method . Clin Biochem 9:35-38, 1976;.
Gibaldi M, Perrier D: Pharmacokinetics . New York, Marcel Dekker Inc, 1975;, pp 293-296.
Snedecor GW:  Comparisons factorial arrangements of treatments , in Statistical Methods , ed 5. Ames, Iowa State College Press, 1956;, pp 329-333.
Kutt H:  Interaction of antiepileptic drugs . Epilepsia 16:393-402, 1975;.

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