• Archives of Pharmacal Research
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• 제21권4호
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• pp.411-417
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• 1998

In order to investigate the effect of the pretreatment with various doses of diltiazem (DTZ) on the pharmacokinetics of indocyanine green (ICG) at steady state, especially the hepatic blood clearance due to the change of hepatic blood flow, the following experiments were carried out with ICG, a hepatic function test marker, not metabolized in liver and only excreted in bile. The intravenous bolus injection ($3,780\mu\textrm{g}$/kg) and the constant-rate infusion ($10,100\mu\textrm{g}$/kg/hr) of ICG into the left femoral vein were made in order to check the steady-state plasma concentration ($C_{ss} of $10\mu\textrm{g}$/ml) of ICG at 20, 25 and 30 min. Following a 90-min washout period, the intravenous bolus injection (108, 430, 860 and $1,720\mu\textrm{g}$/kg) and the constant-rate infusion (108, 433, 866 and $1,730\mu\textrm{g}$/kg/hr) of DTZ into the right femoral vein were made and the achievement of the steady-state plasma levels ($C_{ss} of 50, 200, 400 and 800 ng/ml) of DTZ were conformed at 60, 70 and 80 min. During the steady state of DTZ, the intravenous bolus injection ($3,780\mu\textrm{g}$/kg) and the constant-rate infusion ($10,200\mu\textrm{g}$/kg/hr) of ICG into the left femoral vein were made and also the steady-state plasma concentration of ICG was checked at 20, 25 and 30 min. The plasma concentrations of DTZ and ICG were determined using a high performance liquid chromatographic technique. At the steady state, the hepatic blood clearance of ICG was obtained from the plasma concentration and blood-to-plasma concentration ratio ($R_B$) of ICG. The pretreatment with various doses of DTZ did not influence the plasma concentrations, $R_B$ and plasma free fraction ($f_p$) of ICG. So the hepatic blood clearance of ICG was independent of concentration of DTZ. The hepatic blood clearance of ICG could be affected by both hepatic bood flow and hepatic intrinsic clearance. But there was no change of the hepatic blood clearance of ICG between the control and the DTZ-pretreated rats in this study. So it may be suggested that DTZ does not influence hepatic blood flow.

• Archives of Pharmacal Research
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• 제28권1호
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• pp.115-119
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• 2005

The clearance of ICG, a known hepatic blood flow marker was investigated in rats in order to examine whether DDB-S influences hepatic blood flow. The effect of DDB-S on the protein binding and blood-to-plasma partition of ICG was measured. The steady-state plasma concentration of ICG was monitored before and after co-administration of various concentration of DDB-S, and ICG clearance was estimated from the steady-state concentration and the infusion rate of ICG. There was no significant difference in protein binding and blood-to-plasma partition of ICG with and without addition of DDB-S (10, 20, and 40 ${\mu}g/mL)$. When ICG was infused into DDB-S pretreated rats, the steady-state concentrations of ICG decreased and the calculated ICG clearance increased. However, no dose-dependency of ICG Css on DDB-S Css was observed. Since DDB-S did not affect the protein binding and blood-to-plasma partition of ICG, the increased clearance of ICG with co-administration of DDB-S seems to be due to the increased hepatic blood flow by DDB-S.

• 약학회지
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• 제37권4호
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• pp.383-388
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• 1993

Pharmacokinetics of aucubin, an irdoid glucoside, was compared in rats of experimental hepatic failure(EHF). EHF was induced by CCI$_{4}$ or D-galactosamine pretreatment. This work was designed to find out any differences in the pharmacokinetics of aucubin that may explain the different protective effect of aucubin on CCI$_{4}$- and galactosamine-induced EHF : aucubin reportedly protected CCI$_{4}$-inducing hepatotoxicity effectively, but did not for galactosamine-hepatotoxicity. EHF was induced by intraperitoneal injection Of CCI$_{4}$(0.9ml/kg) or galactosamine(250 mg/kg) to Wistar rats 24 hr before the pharmacokinetic study. The rats were fasted during the 24 hr. Aucubin was iv injected at a dose of 15 mg/kg and the plasma aucubin was assayed by HPLC. There were no significant differences in the pathophysiologies(body weight, liver weight, GTP, hematocrit, blood cell distrbution and plasma protein binding of aucubin) between the two EHF models except GOP which was significantly (p<0.05) higher in CCI$_{4}$-than in galactosamine-EHF. On the other hand, pharmacokinetics of aucubin such as total cleatance(CL$_{t}$), distribution volume at steady-state(Vd$_{ss}$), and mean residence time(MRT) differed significantly(p<0.05) between the models : for example, CL$_{t}$ was increased two fold by CCI$_{4}$, but not by galaclosamine ; Vd$_{ss}$, in galactosamine-EHF was higher than that in CCI$_{4}$-EHF ; MRT was decreased by CCI$_{4}$, but increased conversely by galactosamine. The increase of CL$_{t}$(and decrease of MRT) in rats of CCI$_{4}$-EHF was contrary to the general expectation for the hepatic failure : most of the hepatic failures have been known to decrease CL$_{t}$ of the administered drugs. Whether the difference in the pharmacokinetics is responsible for the different protective effect of aucubin against the two EHF models is of interest. However, much more studies on biliary excretion, urinary excretion, and hepatic uptake in cellular level should be preceded before any conclusions are made on the role of different pharmacokinetics on the different pharmacology of aucubin.