Gender differences in the antidiarrheal effect of zaldaride maleate in rats

The amelioration of secretory diarrhea has been reported after the administ ration of zaldaride maleate (ZAL), a selective calmodulin inhibitor, to mal e rodents, In this study, the antidiarrheal effect of ZAL in female rats wa s compared with that in male rats. In female and male rats, ZAL significant ly ameliorated 16,16-dimethyl prostaglandin E-2-induced diarrhea at doses o f 1 and 3 mg/kg (p.o.), respectively, with ID50, values of 0.7 mg/kg (p.o.) in the females and 10.3 mg/kg (p.o.) in males. In castor oil-induced diarr hea, ZAL also significantly reduced the incidence of diarrhea in female and male rats at doses of 10 and 30 mg/kg (p.o.), respectively. When the same dose of ZAL was given orally to female and male rats, the maximum plasma le vel of this compound was approximately 3 times higher in female rats than i n male rats, In contrast, after intravenous administration of the same dose of ZAL to female and male rats, the total clearance of this compound was s imilar, In an Ussing chamber experiment, the inhibitory action of ZAL on va soactive intestinal polypeptide-induced ion secretion in the colon showed n o difference between female and male rats, In conclusion, the antidiarrheal effect of ZAL in female rats is more potent than that in males, and could be due to the difference in plasma levels of this compound between female a nd male rats after oral administration.