木犀草素的药动学

本文研究了木犀草素(Lut)溶液在兔和大鼠体内的药动学。用荧光光谱法测定兔血浆和尿液中Lut与原儿茶酸(PCA,Lut的一种代谢物)的浓度,以及大鼠胆汁中Lut的含量。根据Lut的多峰药一时曲线建立了一种可定量描述肠肝循环的三室开放模型,并在该模型中增添了振荡项,据此,用自编的非线性算法程序在IBM-PC型微机上拟合和绘制Lut的C-T曲线。求得的主要药动学参数(均值±SD)为:t 1/2(α)和t1/2(β)分别为0.181(±0.1)h和1.66(±0.24)h。转运、重吸收和消除速率常数(k_(12),k_0和k_(10))分别为1.495±0.45h~(-1),0.465±0.08h~(-1)和1.124±0.35 h~(-1)。重吸收率为6.9±2.1％。Vd为1.432±0.45L·kg~(-1)。清除率为588±113μg·kg~(-1)·h~(-1)。家兔12h尿中Lut的累积排泄量约为静注量的37.7％。大鼠6h胆汁中Lut的累积排泄量为给药量的11.2％。比较PCA与Lut的C—T曲线,提示PCA为Lut的一种代谢物。PCA亦经肾排泄。大鼠ig~3H—Lut后迅速吸收,且广泛分布于多种组织,其中以肝和肾组织的放射性同位素含量为最高。

THE PHARMACOKINETICS OF LUTEOLIN

The pharmacokinetics of Luteolin ( Lut ) solution in rabbits and rats was investigated. Lut in plasma, bile and urine as well as protocatechuic acid (which is a product of Lut) in plasma and urine were determined by fluorescence spectrophotometry. A curve with multiple peaks was fitted to the data of plasma concentration versus time, employing a nonlinear program developed with an IBM-PC computer. The results indicated that the data set obtained with 30 mg /kg doses by iv fitted well to a peculiar open 3 compartment model involved in the enterohepatic recirculation of the drug and the undulations of the drug concentration.The essential pharmacokinetics parameters (mean?SD) were as follows; The t1/2 values for the ?-phase and ?-phase were about 0.18?0.01 h and 1.66?0.24 h respectively. The apparent volume of distribution ( Vd) was about 1.43? 0.45 L?kg-1. The reabsorption rate constant ( Ka ) was 0.465? 0.08 h-1 The reabsorption percent ( F' ) was about 6.9? 2.1% . The elimination rate constant was 1.124?0.35 h-1. The clearance was 588?113 ?g?h-1 ?kg-1. This study indicated that Lut was rapidly removed from the blood by both kidney and liver where Lut was excreted by way of the bile into intestine from which it Was reabsorbed. The 12 h urine excretion of Lut in rabbits was in the order of 37.7% of total iv dose. In rats, the 6 h bile excretion of Lut was about 11.2% of that total iv dose. A comparison of the C-T curve of PCA with of Lut suggested that PCA was the one of the products of Lut.In rats, the 3H-Lut orally administered was widely distributed in the tissues, the concentrations being higher in liver and kidney.