| In Vivo |
The brain concentration of KCL-440 is sufficient to inhibit the PARP activity during the intravenous infusion at the rate of 1 mg/kg/h[1]. KCL-440 (over 0.03 mg/kg/h) exhibits neuroprotective effects of KCL-440 in the in vivo cerebral ischemia model[1]. Animal Model: Rat acute cerebral infarction model induced by photothrombotic MCA occlusion[1]. Dosage: 0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg/h. Administration: Intravenously administered at a rate of 0.33 ml/kg/h for 24 h immediately aftercerebral ischemia. Result: The serum concentration of KCL-440 approached steadystate levels within 1 h in rats that were intravenously infused at the rate of 1 mg/kg/h for 6 h. One hour after the initiation of infusion, the serum concentration of KCL-440 is 0.11 μg/mL, which is equivalent to 0.37 μM. The brain:serum concentration ratio after a 6-h infusion at 10 mg/kg/h is 0.8. Led to a dose-dependent reduction in the cerebral infarct size at 24 h after the MCA occlusion.
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