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In this study, the feto-placental transfer or excretion into the milk of SK-896 ([Leu13]motilin-Hse), a new human motilin analogue, were assessed after single intravenous injection of gestation or lactating female rats with 3H-SK-896. Two min after intravenous bolus injection of pregnant rats with 3H-SK-896 on the 12th and 18th day of gestation, respectively, the total radioactivity transferred to fetuses on the 18th day of gestation was higher than that on the 12th day of gestation, but both of them were less than 7% of maternal plasma. Furthermore, no immunoreactive radioactivity was detected 2 min and 30 min after administration in the fetal plasma on the 18th day of gestation, respectively. These results suggested that virtually no SK-896 is transferred to the fetus. After intravenous bolus injection of lactating rats with 3H-SK-896, the total radioactivity in the milk increased with time, reaching maximum 6 h after administration, and thereafter decreased. Although total radioactivity in the plasma was higher in the early stage after dosing, the milk-to-plasma concentration ratio rose with time, reaching 9.27 6 h after dosing. On the other hand, immunoreactive radioactivity was detected in the milk 15 min and 30 min after intravenous bolus injection, respectively, and 30 min after dosing the milk-to-plasma concentration ratio reached a maximum level of 1.59. But the immunoreactive radioactivity in the milk was eliminated rapidly and fell below the detection limit 1 h after dosing. With high performance liquid chromatography analysis of radioactivity in the milk, the peak of 3H-SK-896 was observed.

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Metabolic Fate of SK-896, a New Human Motilin Analogue ([Leu13]motilin-Hse). (III): Feto-Placental Transfer and Excretion into Milk in Rats after Single Intravenous Injection of 3H-SK-896.