Pharmacokinetic Studies of Suplatast tosilate (IPD-1151 T) (I) :Absorption, Distribution and Excretion after Administration of ¹⁴C-Suplatast tosilate (IPD-1151T) to Rats.

Abstract

The absorption, distribution and excretion of suplatast tosilate, (±)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenylcarbamoyl]ethyl]dimethylsulfonium p-toluenesulfonate (IPD-1151T) were studied in rats after a single or repeated administration of ¹⁴C-labeled-IPD-1151T.
1. After oral administration, the blood radioactivity reached the C_max at 8hr and then decreased with half-life of 12day, and the blood-to-plasma level ratio became high. It seems that elmination of radioactivity from blood cell was very slow. It is suggested that absorption of IPD-1151T was affected by food as manifested by the decrease of blood radioactivity in fasting rats.
2. Approximately 87% and 11% of radioactivity was excreted during 72hr after intravenous administration in urine and feces, respectively and corresponding values for oral administration were approximately 26% and 73% in urine and feces.
3. About 9 % and 17% of radioactivity was excreted in bile after intravenous and oral administration, respectively. When the bile was administered, more than 90% of radioactivity present in the bile was reabsorbed. This result suggested the presence of the entero-hepatic circulation.
4. A high radioactivity was found in the intestine, urinary bladder, mesenteric lymph node, pancreas, kidney, seminal vesicle and liver after oral administration, and it disappea red slowly from any tissue.
5. After oral administration, the blood and tissue radioactivities and the excretion of radioactivities in urine and feces did not essentially differ between male and female rats.
6. The blood radioactivity gradually increased during repeated oral administration and on day 27, the blood radioactivity reached a plateau. While there was not any definite accumulation in any particular organ or tissue after repeated administration.
7. After oral administration to pregnant rats, the radioactivity in fetuses were lower than that in maternal organ (liver, kidney, ovary, uterus, amnion and placenta).
8. When administered to lactating rats, the radioactivity was transfered into the milk up to the same level as maternal plasma, and disappeared rapidly from the milk as that in maternal plasma.