Study On Determination Method And Pharmacokinetics Of Chlorogenic Acid In Animals After Mainline

Chlorogenic acid (CHA) is a kind of depside condensed by caffeic acid with quinic acid, which commonly exists in many kinds of plants. It acts as the primary effectual components in lots of Chinese traditional medicine. Researches indicates that Chlorogenic acid has wide biological functions such as treating gallbladder, antibiotics, anti-virus, hemostasis, enhancing leucocyt, decreasing blood-coagulating interval, and increasing the hemoleukocyte, etc. Chlorogenic acid is becoming a hotspot .of international study.The Chlorogenic acid manufacture is the groundwork in exploiture of Chlorogenic acid as inovative drug. In this study, the evaluating method for CHA in biological samples has been established. The pharmacokinetics, distributions feature in vivo, and many other aspects of CHA have been studied. The results of this study can provide reference for clinic trial and further studies.In this study, Content of CHA in bio-samples from beagle's serum and plasma, rats' serum and plasma, rats' tissue and beagle's excreta is assayed by the reversed phase high performance liquid chromatography.The linearity of CHA in serum (or tissue) and excreta is y=0.086x-0.0002 and y=0.0025x+7×l0^<sup>-5, respectively. The precision within-day is 1.18% in serum and 1.05% in excreta; the precision between-day is 2.40% in serum and 1.42% in excreta. The recovery is 102.0% and 100.7%, respectively. Both the lowest detectable concentration is 6.25ng/mL.In this paper, the metabolic transformation, tissue distribution, excretion pathway and protein-binding is investigated. The metabolism status of CHA and the effect on the metabolic enzyme P450 by CHA is indicated primarily.The pharmacokinetics results of CHA are showed as follow:1. The pharmacokinetics of CHA in beagles and in rats both could be fitted with two-compartment model. Ti/2pof CHA after vein injection different doses in beagles. is 44.10min, that in rats is 44.68 min; Vdin beagles is 0.83L/kg, and that in rats is 1.47 L/kg; CL in beagles is 0.006L/min/kg, and that in rats is 0.014 L/min/kg; AUCo-iso in beagle is 875.59, 2531.6, 9007.1 min'mg/L respectively, and AUCoⁱ8o in rats is 347.3, 1149.9, 4132.5 mhrmg/L respectively. Both the pharmacokinetics show linear feature.2. After administration of different doses in rats, the CHA is distributed mainly to kidney, and to liver, lung, heart, muscle, intestinal guts, stomach and fat secondarily. The drug content in tissue is relatively lower than that in serum. That content in tissue is highest in 30 min mostly, but individualy tissue has its highest content in 10 min. And the content decreases to low level after 150min.3. After administration of different doses in beagles dog, CHA is mostly excreted as original forms in urine, and the excretion in dejecta is few. The excretion rate to the administration in urine is 83.4*^ 94.5% and 13.0% respectively; and that in dejecta is 2.847%^ 1.193% and 1.527% respectively.4. The protein-binding rate of CHA after administration of different doses in beagles is 25.6±2^/ck 35.4±1.43% and 38.8±0.72%respectively; while that in rats is 42.4±1.66%> 46.5±0.83%, and 43.7±0.73% respectively.5. The metabolin of CHA is found more in urine than in blood both in beagles and in rats after vein injection. Its total amount is too small to be identified, and the research in that is still on.6. The effect on the active metabolic enzyme P450 by CHA in rats after vein injection is not markedly.