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SK-896 ([Leu13]motilin-Hse) is a new human motilin analogue synthesized by Escherichia coli using a biotechnological method. In this study, the pharmacokinetic properties of SK-896 after a single intravenous injection or during and after a single constant rate intravenous infusion of rats with 3H-SK-896 were assessed. After intravenous bolus injection of male and female rats with 3H-SK-896 at the dose of 4 μg/kg, the plasma levels of immunoreactive radioactivity declined bi-exponentially. No sex difference in pharmacokinetic properties was observed after the intravenous bolus injection. During constant rate intravenous infusion of male rats at the dose of 4μg/kg/h for 20 min, the plasma level of immunoreactive radioactivity increased rapidly, and declined bi-exponentially after the completion of infusion. No significant differences in pharmacokinetic parameters were observed between intravenous bolus injection and intravenous infusion, suggesting that there was essentially no change in the pharmacokinetics by the administration rate. Within 120 h after intravenous bolus injection to male and female rats at the dose of 4μg/kg, 10.9%, 9.55% and 3.84% of administered radioactivity were excreted into urine, feces and expired air in males, against 22.7%, 13.1% and 5.38% in female rats, respectively. Serum protein binding of 3H-SK-896 was 91.4-94.2% in dog, 93.6-96.6% in rat and 96.2-97.0% in human. Binding ratio of 3H-SK-896 to human serum albumin was 84.2-87.0%. Concentration-dependency of 3H-SK-896 binding to serum proteins was not observed over the concentration range studied.

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Metabolic Fate of SK-896, a New Human Motilin Analogue ([Leu13]motilin-Hse). (II): Blood and Plasma Concentration and Excretion in Rats afrter Single Intravenous Injection or Constant Rate Intravenous Infusion of 3H-SK-896.