횐쥐에서 nitrone계 항산화제인 α-phenyl-n-ter-butyl nitrone(PBN)의 뇌 투과성 및 체내동태

The Blood-Brain Barrier Permeability and Pharmacokinetics of Nitrone Based Spin Trapping Agent, α-Phenyl-n-tert-Butyl Nitrone (PBN) in Rats

The nitrone-based free radical trapping reagent, α-phenyl-n-tert-butyl nitrone (PBN) has been proposed as therapeutic agent for stroke. We used this for model drug of development of new drug for neuroprotection. The purpose of this study was to evaluate the blood-brain barrier (BBB) permeability of PBN in Sprague-Dawly (SD) rats. The BBB transport of PBN was investigated in SD rats using internal carotid artery perfusion (ICAP) method at a rate of 4 Ml/min for 15 second. We also obtained pharmacokinetic parameters of PBN using single intravenous injection technique. When we estimated BBB permeability of PBN with ICAP method, the brain volume of istribution of PBN was 60.0 +/- 12.0μg/l. The brain uptake of PBN after IV injection at 120 min was 0.15 +/- 0.01%ID/g. The PBN was transported to the brain through the BBB well in rats, because PBN is small molecule (MW 177) and lipid-soluble (log P 1.23) compound.