Influence of Phenobarbital on the Hepatic Clearance of Organic Anionic Drugs in Rats - On the Basis of Pharmacokinetics of Indocyanine Green -

Rat에 있어서 Phenobarbital이 유기음이온성 의약품의 간클리어란스에 미치는 영향 - Indocyanine Green의 체내동태를 중심으로 -

The influence of phenobarbital(PB) pretreatment(75mg/kg/day, Lp. for 4 days) on the hepatic clearance of indocyanine green(ICG) as a model compound of organic anionic drugs was investigated in rats in order to elucidate the relative contributions of change in the hepatic blood flow versus increase in the hepatic intrinsic activity to remove ICG due to PB pretreatment. ICG(1mg/kg) was injected single bolus via femoral or portal vein to the control and the PB-pretreated rats. The initial hepatic uptake clearance$(V_{d.c.}K_{12})$ obtained from plasma concentration-time data was increased by $38.4\% in the PB-pretreated rats, which may be due to the increased hepatic blood flow by PB pretreatment. Using a pharmacokinetic approach, hepatic blood flows were estimated of 67.5ml/min/kg in control rats and 91.9ml/min/kg in PB-pretreated rats. They were in good agreement with other's blood flow estimates observed experimentally. It may be concluded that the $38\%$ increased initial hepatic uptake clearance of ICG was due to the $36\%$ increased hepatic blood flow with phenobarbital, and that the increased hepatic blood flow and the activated hepatic intrinsic clearance with phenobarbital contributed to $49\%\;and\;51\%$ of the increased systemic clearance of ICG, respectively.