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

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)

• Authors: C I Valencia, B A Catto, E H Fairchild, S B Wilson, N C Maramba, L T Webster Jr
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 230 Issue 1 Pg. 133-40 (Jul 1984) ISSN: 0022-3565 [Print] United States
• PMID: 6547741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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