| Summary: | 碩士 === 台北醫學院 === 藥學研究所 === 88 === Abstract
Geraniin, one of the major components isolated from Geranium thunbergii Sieb. et Zucc., is a widely distributed ellagitannin with a dehydrohexahydroxydiphenoyl (DHHDP) moiety. In previous studies, geraniin has been demonstrated to antidiarrhea and cytoprotective effect; potent cytotoxicity in melanoma tumor cells with ED50=0.35μg/ml; enhancement of phagocytosis and acid phosphatase activity in macrophage; anti-lipid peroxydation in mitochondria; lowing the GOT, GPT, LPO, TG and free fatty acid in rat; anti-inflammatory, antinociceptive effect, cytoprotective effect and anti-hypertensive action in rat. Although several pharmacological effects has been reported, but the pharmacokinetics of geraniin has not been studied.
An accuracy, simple and specific analytical method based on HPLC was developed to detect the geraniin in the biological sample firstly. A phenyl reversed phase column with UV detection at 280nm was used in chromatographic separation. Under these chromatographic conditions, the calibration curve of plasma shows a good linearity within the concentration range of 0.1mg to 100mg/ml (Y=0.0008+ 0.0488X, r2=0.9922). The validations of this analytical method are within the acceptable criteria.
The pharmacokinetics of geraniin was studied by intravenous administration of three different doses (1, 2, 5mg/kg) to six rabbits, respectively. The plasma concentration-time profiles of geraniin could be described by a bi-exponential equation with each dose. The elimination half-lives are 70.63*14.65, 81.76*15.04, 81.34*4.46 minutes, and the systemic clearance are 2.08*0.81, 2.18*0.62, 2.89*0.64 ml/min./kg. These data show a linear pharmacokinetic property of geraniin in rabbits between 1~5mg/kg with intravenous administration. The area under the curves (AUC) calculated from time zero to infinite are 551.77*232.72, 985.23*296.15, 1819.59*504.75 mg*min/ml. A good linear relationship between dose and AUC is obtained, Y=297.5460+307.9935X, r2=0.7081, P<0.001.The renal clearance are 0.18*0.06, 0.12*0.07 and 0.15*0.05 ml/min/kg, they are 9.20*3.52%, 5.14*2.04 % and 5.42*1.64 % of total clearance, respectively. It indicated that the nonrenal clearance of geraniin play an important role in elimination.
After oral administration of geraniin 5, 50, 100, 250mg/kg to rabbits, the concentration of geraniin in plasma is lower than 0.1mg/ml. According to the stability test, geraniin is quite unstable in gastric acid and basic conditions. It is suggested that unstable in gut results in poor absorption after oral administration of geraniin.
From these data in above, geraniin shows a dose-independent pharmacokinetic property with mainly nonrenal clearance elimination after I.V. administration of 1~5mg/kg geraniin to rabbits. The unstability of geraniin in gut may be the major reason of poor absorption after P.O. administration of 5~250mg/kg geraniin to rabbits.
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