Nishimura M, Yamaoka K, Yasui H, Naito S, Nakagawa T
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Biol Pharm Bull. 1994 Sep;17(9):1301-4. doi: 10.1248/bpb.17.1301.
The local hepatic disposition of BOF-4272, a newly developed xanthine oxidase (XO)/xanthine dehydrogenase (XDH) inhibitor, was evaluated in the rat perfusion system following pulse input of the drug into the portal vein. The elution time profiles from the liver into the hepatic vein were analyzed by dispersion models. The disposition of BOF-4272 through the rat liver was represented by a two-compartment dispersion model based on the Akaike's Information Criterion (AIC). The area under the concentration time curve (aucH) of BOF-4272 was proportional to the dosing amount, and the mean transit time was constant from 62.5 up to 500 micrograms/liver, which demonstrates that the local hepatic disposition of BOF-4272 is linear in this dosing range. The local disposition parameters were precisely estimated at the dosing amount of 250 micrograms/liver using several rats. These parameters in the dispersion model were correlated to the local moment characteristics. The hepatic recovery ratio (FH) was 22.8 +/- 3.2% and the mean transit time (tH) was 0.112 +/- 0.008 min, which show that the influx of BOF-4272 into the liver is efficiently large.
在将一种新开发的黄嘌呤氧化酶（XO）/黄嘌呤脱氢酶（XDH）抑制剂BOF-4272经门静脉脉冲输入大鼠灌注系统后，评估了其在肝脏的局部处置情况。通过分散模型分析了从肝脏到肝静脉的洗脱时间曲线。基于赤池信息准则（AIC），用两室分散模型描述了BOF-4272在大鼠肝脏中的处置情况。BOF-4272的浓度-时间曲线下面积（aucH）与给药量成正比，在62.5至500微克/肝脏的剂量范围内，平均通过时间恒定，这表明在此给药范围内BOF-4272在肝脏的局部处置呈线性。使用几只大鼠在给药量为250微克/肝脏时精确估算了局部处置参数。分散模型中的这些参数与局部矩特征相关。肝脏回收率（FH）为22.8±3.2%，平均通过时间（tH）为0.112±0.008分钟，这表明BOF-4272向肝脏的流入量很大。
