Metabolic Fate of Human Urinary Kallidinogenase (SK-827) (6): Plasma Concentration after Intravenous Injection or Constant Rate Intravenous Infusion to Dogs and Rabbits
1994 Volume 9 Issue 1 Pages 83-96
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1994 Volume 9 Issue 1 Pages 83-96
Pharmacokinetics of SK-827 was studied in dogs and rabbits after intravenous injection or after constant rate intravenous infusion of SK-827. Plasma levels of SK-827 were determined by sandwich enzymeimmunoassay.
1. After a single intravenous injectio n of SK-827 to dogs at doses of 0.649 ?? 6.25×10-3 PNAU (p-nitroaniline unit) /kg, the plasma levels declined bi-exponentially. The plasma half-lives of the rapid phase and slower phase after intravenous injection of SK-827 (6.25×10-3 PNAU/kg) were about 3 min (t1/2α) and 40 min (t1/2β), respectively.
2. During single constant rate intravenous infusion of SK-827(1.67 ?? 15×10-3 PNAU/kg for 30 min) to dogs, the plasma levels increased rapidly. After stopping the infusion of SK-827, the plasma levels declined bi-exponentially similar to that after intravenous injection. The AUC0-∞ values after intravenous infusion of SK-827 and C29 (concentration at 29 min after starting the infusion) were proportional to the dose and there were no dose-related changes in the mean residence time (MRTinf), plasma clearance (Clp) and steady-state distribution volume (Vdss), indicating that the plasma levels of SK-827 can be described by the linear pharmakokinetic model.
3. During repeated injec tions of SK-827 to dogs at the dose of 5×10-3 PNAU/kg for 7 days, the plasma levels at 90 min after each injection remained almost constant from the first day. There were no differences in the plasma half-lives of β phase between single and repeated injection (for 4 or 7 days)
4. After a single intravenous injection of SK-827 to rabbits at do ses of 1.67 ?? 15×10-3 PNAU/kg, the plasma levels declined bi-exponentially. The plasma half-lives of the rapid and slower phase were about 5 min (t1/2α) and 120 min (t1/2β) . There were no changes in the values of MRT, Clp and Vdss, indicating that the plasma levels of SK-827 followed the linear pharmakokinetic model.
5. During a single constant rate intravenous infusion of SK-827(5×10-3 PNAU/kg for 30 min) to rabbits, the plasma levels increased rapidly, and declined bi-exponentially after stopping the infusion. The Vdss values and Clp values after intravenous infusion were not different from those after intravenous injection.
