Concentration-time course of niridazole and six metabolites in the serum of four Filipinos with Schistosoma japonicum infection.
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)
D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000097:blood; D007166:Immunosuppressive Agents / Q000097:blood; D007700:Kinetics; D008297:Male; D009560:Niridazole / Q000031:analogs & derivatives / Q000097:blood*; D012549:Schistosoma japonicum; D012552:Schistosomiasis / Q000097:blood*; D013859:Thiocarbamates / Q000097:blood; D013997:Time Factors
D007093:Imidazoles; D007166:Immunosuppressive Agents; D013859:Thiocarbamates; C026957:1-thiocarbamoyl-2-imidazolidinone; C040636:4-ketoniridazole; C029690:4-hydroxyniridazole; C042240:4,5-dehydroniridazole; D009560:Niridazole