Absorption, distribution and metabolism of clioquinol in clioquinol-sensitive and -resistant neonatal rats.
Three types of rats with respect to sensitivity to clioquinol have been identified, the highly sensitive (S-rat), the intermediately sensitive, and the resistant (R-rat). In a toxicity test that lasted for 20 d after birth, the difference in sensitivity to clioquinol between S- and R-rats was confirmed by repeated subcutaneous administration of a clioquinol suspension prepared with polysorbate 80 (clioquinol dose of 150 or 300 mg/kg/d). Plasma and tissue concentrations of clioquinol and the rate of metabolism of the drug in neonatal S- and R-rats were measured. Plasma concentration of clioquinol in 1-d-old S-rats after a single subcutaneous administration was higher than that in the same age R-rats and the area under the mean plasma concentration-time curve for the S-rats was approximately twice that for the R-rats. In addition, clioquinol concentrations in liver, kidney and brain of S-rats at 9 h after the administration were more than twice those of the R-rats. From the experiments on the formation of clioquinol glucuronide and sulfate with 9000 g supernatant fraction of liver, it was suggested that the difference in the plasma concentration after the administration may be responsible for the difference in the metabolizing rate of clioquinol.
D000818:Animals; D000831:Animals, Newborn; D007464:Clioquinol / Q000378:metabolism* / Q000633:toxicity; D004351:Drug Resistance; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006912:Hydroxyquinolines / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013464:Sulfuric Acids / Q000378:metabolism; D014018:Tissue Distribution
D005965:Glucuronates; D006912:Hydroxyquinolines; D013464:Sulfuric Acids; D007464:Clioquinol