Sex difference of the metabolic disposition of clioquinol in rats.

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Abstract
The order of plasma levels of clioquinol and its conguates in male rats after intraduodenal administration of 32.7 .mu.mol/kg dose of clioquinol was clioquinol sulfate (C-Sul) > clioquinol glucuronide (C-Glu) .mchgt. clioquinol, whereas that in female rats was C-Glu > C-Sul .mchgt. clioquinol. Total (urine + bile) recovery was almost the same among male and female rats. The percentage of excretion amounts of C-Sul (urine + bile) to the total excretion amounts for 24 h in male rats after intravenous administration of clioquinol was about twice that in female rats, while the percentage of excretion amounts of C-Glu to the total excretion amounts in male rats was smaller than that in female rats. In intravenous administration of 16.4 .mu.mol/kg dose of C-Glu, C-Sul and clioquinol other than C-Glu were found in bile and urine of male and female rats. The percentage of excretion amounts of C-Sul and C-Glu (urine + bile) to the total excretion amounts was similar among male and female rats, respectively. In intravenous administration of 16.4 .mu.mol/kg dose of C-Sul, C-Glu and clioquinol other than C-Sul were found in bile and urine of male and female rats, and the percentage of excretion amounts C-Sul (urine + bile) to the total excretion amounts in male rats was 1.3 fold that in female rats. From the examination of the in vitro conjugation reaction, the formation rate of C-Glu in the small intestine was approximately same along male and female rats, whereas C-Glu and C-Sul formation rates in male rats were about twice those in female rats, respectively. From the similarity of the extent of the glucuronidation in the small intestine among male and female rats, one reason for the sex difference in the excretion of the two conjugated metabolites at the intraduodenal administration of clioquinol may be due to the difference in sulfation in the liver.