Studies On Pharmacokinetics Of Salvianolic Acid B And Drug-drug Interaction

BACKGROUND:Complex Salvia Miltiorrhiza prescription with Salvia Miltiorrhiza,notoginseng and borneol.The modern preparation possesses the activities in expanzing of coronary artery,increasing coronary blood flow,decreasing heart rate,improving microcirculation,myocardial ischemia,cardiovascular and cerebrovascular acute ischemic symptoms and ECG changes,inhibiting platelet aggregation,and platelet release reaction,reducing blood viscosity,reducing blood fat,and preventing thrombosis.It is used for the treatment of coronary heart disease and angina pectoris.The preparation is contented of salvianolic acids of Salvia miltiorrhiza Bunge(including salvianolic acid A,salvianolic acid B,rosmarinic acid,caffeic acid,Protocatechualdehyde,protocatechuic acid,Danshensu),triterpenoid saponins of sanchi(including ginsenoside Rb1,Rd,Rgl and notoginsenoside R1),and borneols.It is important that investigation of the drug-drug interaction in pharmacokinetics of the principle components in Complex Salvia Miltiorrhiza for the modern preparation of traditional Chinese medicine.OBJECTIVES:In order to comprehensively profile the pharmacokinetic characteristics of Complex Salvia Miltiorrhiza prescription and to investigate the drug-drug interactions in pharmacokinetics,an established liquid chromatography-mass spectrometry(LC/MS)method was applied to determine the pharmacokinetic parameters of the principle components of Complex Salvia Miltiorrhiza prescription and drug-drug interactions in pharmacokinetics.METHODS:The liquid chromatography-mass spectrometry methods were established and validated to determine the levels of aqueous compositions of Complex Salvia Miltiorrhiza prescription,including salvianolic acid A,salvianolic acid B,rosmarinic acid,caffeic acid,Protocatechualdehyde,protocatechuic acid,Danshensu and salvianolic acid B major metabolites.Their pharmacokinetics was identified through rats.Furthermore,the pharmacokinetics and distribution of Salvianolic acid B(SAB)were determined from rats after oral administrations and co-administration of SAB with Borneol,metoprolol and butyl phthalide.RESULTS:1.The metabolism is relatively fast for the aqueous components of Complex Salvia Miltiorrhiza prescription,presented by SAB.The parent compounds were not found in the plasma of rats at 4 h after oral administration.The distribution of SAB decreased in lung,kidney,liver and heart,subsequently.SAB was excluded out quickly without any accumulation.2.When borneol was administrated with SAB,the absorption of SAB was enhanced at different levels,which were corresponding to the different doses of borneol.Composition elevated the maximum circulating level of SAB as well as the quick clearance.Thus the drug accumulation was not found in the major organs.3.When SAB was administrated with metoprolol,the metoprolol blood level of was significantly elevated and the metoprolol metabolite,metoprolol acid,was decreased,which was caused by the competition of CYP450.While SAB was administrated with butyl phthalide,their pharmacokinetics were not found significant changes in the compared study.CONCLUSION:An LC/MS method was established and applied for the investigations of pharmacokinetics,distribution and the metabolism of SAB.The pharmacokinetic characteristics of SAB was determined post the simultanecus administration with borneol.Metoprolol and butyl phthalide were individually dosed with SAB to investigate the potential interactions between drug-drug or drug-food.This study provides references for the modernization of Complex Salvia Miltiorrhiza prescription.