Therapeutic Drug Monitoring Of Square--Clinical Pharmacokinetics And Therapeutic Effect Of Coronary Heart NoⅡ Decoction

For further accumulating technique experience ,improving the whole quality of control and affording the valuable foundation data for next large-scale clinical trial research,we have observed the therapeutic effect of Coronary Heart NoⅡ Decoction(CHNⅡ) in treating patients of coronary artery disease with blood stasis,and in order to test and study the Syndrome and Treatment Pharmacokinetics(S-TPK), ferulic acid(FA) as a key measurement substance in square including Ligusticum wallichii, we have studied its pharmacokinetical character in patients of coronary artery disease with blood stasis from oral coronary heart NoⅡ decoction.The main results were as follows. First, in the research of therapeutic effect of CHNⅡ, fifty patients were divided into two groups randomly ,twenty six patients with CHNⅡ and twenty four patients with Nitorol were chosen and treated for 15 days.Results:(1)Both of these two medications had effect to alleviate angina and improve ischemic S-T segment changes in ECG,the difference were insignificant；(2) CHNⅡcould improve abnormal hemorheology obviously, lower serum total cholesterol(TC), low density lipoprotein- cholesterol(LDL-C) and endothelin-1(ET). Second, in the research of Pharmacokinetics of ferulic acid(FA), first ten patients of coronary artery disease with blood stasis were chosen and the patients' serums after oral CHNⅡwere taken at the time of 5,10,15,30,60,90,120min. Then a Waters HPLC instrument with Kromasil C18 column was used. The mobile phase was amixture of methanol, acetic acid and water in a ratio of 36.4:63:0.6(V/V/v) at a flow rate of 1.0mL/min,the detector was set at 322nm. Phydroxyben- zaldehyde was used as internal standard. The serum sample containing FA was extracted and deproteinized with acetonitrile. Applying this method(HPLC) was to determine the FA in patients of coronary artery disease with blood stasis.At last the concentration of FA was fitted and pharmacokinetic parameters were calculated with a 3p97 program on a COMPAQ 386 computer . RESULTS: A two-compartment model was adopted in FA plasma concentration-time data analysis.The pharmacokinetic parameters are as follows:Ka=(0.09±0.06)min-1,Ke=(0.022±0.005)min-1,T1/2α=(9.9±4.2)min-1,T1/2β=(33.9±10.8)min-1,Cmax=(33.2±12.5)μg.L-1,AUC=(2452±504)μg.min-1.L-1. Conclusion:CHNⅡhas significant effect on patients of coronary artery disease with blood stasis,it may be alleviate angina through many kinds of ways that we are not certain. Regarding it as measurement index and material basis about pharmacodynamic in body to carry out therapeutic drug mionitoring, the pharmacokinetical character of FA may be apply a new idea for CHNⅡ's clinical study and provide the foundation data for further confirming the authenticity of hypothesis- the Syndrome and Treatment Pharmacokinetics(S -TPK).