Metabolic Fate of SK-896, a New Human Motilin Analogue ([Leu13]motilin-Hse). (I): Distribution and Accumulation in Rats after Single or Repeated Intravenous Injection of 3H-SK-896.

Abstract

In this study, the distribution and accumulation of SK-896 ([Leu13]motilin-Hse), a new human motilin analogue, were assessed after single or repeated intravenous administration of rats with3H-SK-896. Following intravenous bolus injection of male rats with 3H-SK-896, the percentage of plasma immunoreactive radioactivity to plasma total radioactivity was 88.9% at 2 min, 50.9% at 15 min and 17.2% at 30 min, respectively. The highest radioactivity was found in the kidney at 2 min after administration, when most of the plasma total radioactivity was immunoreactive. The levels of radioactivity in the cerebrum, cerebellum, and testis were less than 3% of that in the plasma, and the radioactivity in the other tissues except for kidney were less than 30% of that in the plasma. These results suggested that little 3H-SK-896 and its immunoreactive metabolites transferred to the tissues except for kidney. In female rats, the distribution profiles of the radioactivity after intravenous injection were the same as those of male rats. Also there was no localization of radioactivity in the genital organs, indicating that there was no sex difference in tissue distribution of 3H-SK-896 after intravenous injection to rats. After multiple intravenous bolus injections (SK-896 was given once a day for 6 days and 3H-SK-896 was given on the 7th day) to male rats, the percentage of plasma immunoreactive radioactivity to plasma total radioactivity was 92.5% at 2 min, 50.6% at 15 min and 17.6% at 30 min, respectively, the same as with a single administration. There were no differences in the tissue distribution profiles of radioactivity between single and repeated intravenous bolus injections.