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Effect of concomitant isoniazid administration on determination of acetylator phenotype by sulphadimidine

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Summary

The influence of concomitant administration of isoniazid (INH) on the acetylation of sulphadimidine has been studied in 6 healthy volunteers, previously identified as having the fast acetylator phenotype. INH was administered in a slow release form (500 mg tablet) 1 hour before the sulphadimidine. Acetylation of sulphadimidine was measured in plasma 6 h after its intake and in urine collected between 5 and 6 hours. INH significantly decreased the acetylated fraction of sulphadimidine in plasma from 69.0 to 54.0 and in urine from 85.9 to 81.2%. This was reflected in a significantly higher plasma concentration of unconjugated sulphadimidine and reduced urinary excretion of acetylated sulphadimidine. It is concluded that concomitant administration of INH inhibits acetylation of sulphadimidine. Fast acetylators at the border line of discrimination, may be misclassified if phenotyped with sulphadimidine during concomitant administration of INH.

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References

  1. 1.

    Evans DAP, Manley KA, McKumick VA (1960) Genetic control of isoniazid metabolism in man. Br Med J 2: 485–491

  2. 2.

    Clark DWJ (1985) Genetically determined variability in acetylation and oxidation. Therapeutic implications. Drugs 29: 342–375

  3. 3.

    Dubbels R, Kattner E, Sell-Maurer D, Schloot W (1980) Sulfadimidine and isoniazid loading in man and laboratory rats. Arzneimittelforsch/Drug Res 30 (II): 1574–1579

  4. 4.

    Evans DAP (1969) An improved and simplified method of detecting the acetylator phenotype. J Med Genet 6: 405–407

  5. 5.

    Bratton AC, Marshall EK Jr (1939) A new coupling component for sulphanilamide determination. J Biol Chem 128: 537

  6. 6.

    Timbrell JA, Wright JM, Smith CM (1977) Determination of hydrazine metabolites of isoniazid in human urine by gas chromatography. J Chromatogr 138: 165–172

  7. 7.

    Du Souich P, McLean AJ, Stoeckel K, Ohlendorf D, Gibaldi M (1979) Screening methods using sulfamethazine for determining acetylator phenotype. Clin Pharmacol Ther 26: 757–765

  8. 8.

    Talseth T, Landmark KH (1977) Polymorphic acetylation of sulphadimidine in normal and uraemic man. Eur J Clin Pharmacol 11: 33–36

  9. 9.

    Du Souich P, Lalka D, Slaughter R, Elvin AT, McLean AJ (1979) Mechanisms of nonlinear disposition kinetics of sulfamethazine. Clin Pharmacol Ther 25: 172–183

  10. 10.

    Platzer R, Küpfer A, Bircher J, Preisig R (1978) Polymorphic acetylation and aminopyrine demthylation in Gilbert's syndrome. Eur J Clin Invest 8: 219–223

  11. 11.

    Glatthaar E, Gärtig D, Stander MF, Kleeberg HH (1977) Isoniazid levels in black patients dosed with a matrix preparation (tebesium). Prax Pneumol 31: 885–889

  12. 12.

    Ylitalo P, Auterinen L, Marttinen A, Koivula T (1984) Acetylator phenotyping with sulphadimidine in patients receiving isoniazid. Int J Clin Pharmacol Res IV: 141–144

  13. 13.

    Gilman AG, Goodman LS, Gilman A (ed) (1980) The pharmacological basis of therapeutics, 6th ed. Macmillan, New York Toronto London

  14. 14.

    Tiitinen H (1969) Isoniazid and ethionamide serum levels and inactivation in Finnish subjects. Scand J Respir Dis 50: 110–124

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Zysset, T., Peretti, E. Effect of concomitant isoniazid administration on determination of acetylator phenotype by sulphadimidine. Eur J Clin Pharmacol 30, 463–466 (1986). https://doi.org/10.1007/BF00607961

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Key words

  • sulphadamine
  • isozianid interaction
  • acetylator phenotyping