Pharamacokinetics Study Of Compounds Chinese Gallnut

Compounds Chinese gallnut is a kind of fishery drug to prevention and cure aquatic Livestock's bacteroidal disease. There are a lot of efficient components as gallic acid, tannin, anthraquinone and flavonoid, which have the effect to antibiotic, detoxificate and restorate. There have been no studies about the pharamacokinetics of Compounds Chinese gallnut in aquatic Livestock, and the effect of the drug on the Cytochrome P450—a series of impotant drug metabolizing enzymes.This dissertation established the method for mensurating the content of efficient components in Compounds Chinese gallnut and Chinese gallnut ,got the content of gallic acid and baicalin,studied the pharamacokinetics process of the two drugs in crucian while choose the gallic acid as the target medicine ,and explored the effect of the two drugs on the liver and kidney Cytochrome P4503A activity.1. Determination of efficient components in Compounds Chinese gallnutTo determine the main efficient components in Compounds Chinese gallnut and Chinese gallnut by HPLC, gradient elution using the methanol-0.1% phosphoric acid (pH=2.8) solvent system and detected at 280nm.The content of gallic acid in Chinese gallnut is 3.52%, the extracton recovery is 98.8±2.1%, RSD is 2.17%, while the contents of gallic acid and baicalin in Compounds Chinese gallnut are 1.89% and 0.28%, the extracton recovery are 96.9±3.1% and 105.7±4.4% , RSD are 2.17% and 4.18% respectively.2. The pharamacokinetics study of Compounds Chinese gallnut in crucianTo established the method to detect the gallic acid in crucia's different tissues by HPLC, the drugs were given through mouth . Choosing the gallic acid as the target, the isocratic elution was performed with methanol-0.1% phosphoric acid (pH=2.8)(20:80,v/v) at a flow rate of 0.5mL/min, detected at 273nm.Under above conditions ,the average recovery of gallic acid in crucian's different tissures was good ,the RSD was in the limited range .On the base of above analysis methods ,the pharmacokinetics was studied after a single dose of Compounds Chinese gallnut and Chinese gallnut separately,the dose was 20mg/kg gallic acid. In the two group, the curves between plasma concentration of drug and time could be described by open two-compartment model ,the equations were C=39.159e^-0.087t+22.465e^-0.087t, r=0.928, C=75.601e^-0.294t+10.368e^-0.038t, r=1, respectively.In Compounds Chinese gallnut group, the time of reaching peak after medicine (Tmax)and the peak concentration (Cmax)were plasma 1h, 70.513mg/L,liver lh, 32.404mg/L,kidney2h, 28.512mg/L; the t1/2(a),and t1/2(6) were 8.01 h and 8.012h. In Chinese gallnut group.the time of resching peak after medicine (Tmax)and the peak concentration (Cmax) were plasma lh, 58.729 mg/L,liver 1h,28.499mg/l, kidney 2h, 19.755mg/L, the t1/2(a) and t1/2(B) were 2.356 h and 18.152h.3. The effect of Compounds Chinese gallnut on the Cytochrome P4503A in crucianThe microsome of tissures were made by different centrifugation to measure the CYP4503A activity after being given medicine through mouth . The fishes were separated into four groups by diffent kinds of drugs and different doses , In the 3 day,the 7day and the 10 day.,we got the tissues. The result: Compared to the control group, the activity of CYP3A in liver of Compounds Chinese gallnut 30 mg/kg and gallnut 30 mg/kg were decreased significiantly (P＜0.05),and in the 10 d, the activity of the two groups were decreased sharply (P＜0.01), while the activity of CYP3A in liver of Compound Chinese gallnut 10 mg/kg was no change and there were no significiant change of CYP3A in kidney in differet groups .In conclusion,Compound Chinese gallnut and Chinese gallnut could inhibit the Cytochrome P4503A activity in crucian liver ,and the intensity of inhibition increseases with the time of administration and the dose of drugs.