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

Eur J Clin Pharmacol. 1986;30(4):463-6. doi: 10.1007/BF00607961.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adult
  • Biotransformation
  • Drug Interactions
  • Female
  • Humans
  • Isoniazid / pharmacology*
  • Kinetics
  • Male
  • Phenotype
  • Sulfamethazine / blood
  • Sulfamethazine / metabolism*
  • Sulfamethazine / urine

Substances

  • Sulfamethazine
  • Isoniazid