Concentration-time course of niridazole and six metabolites in the serum of four Filipinos with Schistosoma japonicum infection

J Pharmacol Exp Ther. 1984 Jul;230(1):133-40.

Abstract

Niridazole and six of its metabolites have been quantitated by high-pressure liquid chromatography in sera of four male Filipino patients with mild Schistosoma japonicum infections given single oral doses of niridazole (15 mg/kg) on two occasions 10 days apart. Of the five oxidative metabolites measured, 4-hydroxyniridazole and 4-ketoniridazole achieved the highest concentrations, reaching peak values of 0.9 +/- 0.3 microgram/ml of serum (mean +/- S.D., n = 4) and 0.7 +/- 0.1 microgram/ml of serum within 1 to 4 hr. 4-Ketoniridazole achieved peak serum levels 1 hr after the other oxidative metabolites in three of four patients and was the predominant metabolite in the serum of all patients 6 to 10 hr after dosing. By 24 hr, both 4-ketoniridazole and 4-hydroxyniridazole had largely disappeared from the serum. Niridazole and three other oxidative metabolites, 4,5-dihydroxyniridazole, 5-hydroxyniridazole and 4,5-dehydroniridazole, appeared within 1 hr in serum but failed to exceed 0.4 microgram/ml; none of these compounds were detected in the 24-hr serum samples. The pharmacokinetic pattern of niridazole and the oxidative metabolites showed marked interindividual variation but was quite reproducible in the same individual studied 10 days later. 1-Thiocarbamoyl-2-imidazolidinone was analyzed in serum samples by a different high-pressure liquid chromatographic procedure. This reductive metabolite attained maximal levels of 50 to 150 ng/ml of serum 6 to 12 hr after drug administration and remained at 40% or more of its peak concentration even after 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Chromatography, High Pressure Liquid
  • Humans
  • Imidazoles / blood
  • Immunosuppressive Agents / blood
  • Kinetics
  • Male
  • Niridazole / analogs & derivatives
  • Niridazole / blood*
  • Schistosoma japonicum
  • Schistosomiasis / blood*
  • Thiocarbamates / blood
  • Time Factors

Substances

  • Imidazoles
  • Immunosuppressive Agents
  • Thiocarbamates
  • 1-thiocarbamoyl-2-imidazolidinone
  • 4-ketoniridazole
  • 4-hydroxyniridazole
  • 4,5-dehydroniridazole
  • Niridazole