Pharmacokinetic Studies of Suplatast tosilate(IPD-1151T). (IV). Dose dependency and sex difference of Suplatast tosilate(IPD-1151T) in Rats.

Abstract

The dose-dependent pharmacokinetics of suplatast tosilate, (±)-[2-[4-(3-ethoxy-2-hydroxypropoxy) phenylcarbamoyl]ethyl]dimethylsulfonium p-toluenesulfonate(IPD-1151T) after oral administration to male rats at dose of 10, 100, 1000mg/kg, and the sex-related disposition of IPD-1151T were studied after oral (100mg/kg) or intravenous administration of M-1 (6.6 mg/kg). 1. After oral administration of IPD-1151T to male rats, the Cmax and AUC0-t of unchanged IPD-1151T base (IPD-1151T base) in the plasma and the quantity of IPT-1151T base excreted in urine and feces were increased in proportion to administered dose. These suggested that disposition of IPD-1151T base was independent of dose. 2. After oral administration of IPD-1151T to female rats, the AUC0-t of IPD-1151T base in female rats was 1.6 times higher than that in male rats, however Cmax of IPD-1151T base in female rats was of same level as that in male rats. The amount of IPD-1151T base excreted to urine in female rats was similar to that in male rats. From these results, it seemed that disposition of IPD-1151T base did not essentially differ between male and female rats. 3. In order to clarify sex difference in the IPD-1151T disposition, the pharmacokinetics of M-1, which was the first metabolite gradually generated from IPD-1151T base, was studied. After intravenous administration of M-1 to male and female rats, plasma clearance, t1/2 and AUC0-∞ of M-1 in plasma were similar in male and female rats, respectively. It suggested that there was no essentially difference between male and female rats at the degree of M-1 metabolisms when IPD-1151T was administered.