1998 Volume 13 Issue 1 Pages 28-35
We have investigated a linearity and animal species-difference of plasma concentration-time profile of ONO-5046 and its metabolite (M-1) after intravenous administration of ONO-5046·Na to rats and dogs. The following results were obtained.
1. Following intravenous bolus administration of ONO-5046·Na at the doses of 1 and 5 mg/kg to male rats, plasma concentrations of the unchanged drug at 2 min were, respectively, 10.33 and 33.61 μg/ml, and did not increase in a dose-dependent manner. On both doses, t1/2 (5-30 min) of the unchanged drug was approximately 7 min, but CLtotal and Vss obtained from the plasma concentration-time profile increased with the dose.
2. Following intravenous bolus administration of ONO-5046·Na at the doses of 1 and 5 mg/kg to male dogs, t1/2 (5-30 min) of the unchanged drug was approximately 5 min. The AUC0→∞ of unchanged drug increased with the dose.
3. Following intravenous infusion of ONO-5046·Na for 2 hr at the doses of 1 and 10 mg/kg/hr to male rats, plasma concentrations of the unchanged drug reached the steady-state levels within 1 hr, and steadystate levels (C120 min) were 2.29 and 22.05 μg/ml, increased in a dose dependent manner. The plasma concentration (C120 min) of the metabolite (M-1) were 2.02 and 17.81 μg/ml, increased in a dose dependent manner. These results could be explained the linearity at the range of these doses.
4. Following intravenous infusion of ONO-5046·Na for 2 hr at the doses of 1 and 10 mg/kg/hr to male dogs, plasma concentrations of the unchanged drug reached the steady-state levels within 30 min, and steady-state levels (C120 min) were 1.14 and 13.24 μg/ml, increased in a dose dependent manner. CLtotal of the unchanged drug in the dog was approximately twice of that in rats. The plasma concentration (C120 min) of the metabolite (M-1) were 0.40 and 5.40 μg/ml, increased in a dose dependent manner. These results could be explained, similarity to the rats, the linearity at the range of these doses.
