Research on Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin Based on the Metabolic Enzyme and PK-PD Model
试验速览
- 阶段
- 不适用
- 入组人数
- 18
- 主要终点
- Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.
研究概览
简要总结
The combination of anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease. However, the material foundation, effective mechanism and drug-drug interaction is still not clear. In order to solve the puzzle of rational use of Joint application by TCM and Western Medicine(WM),investigators conduct a research on mechanism of drug-drug interaction between salvianolate injection and aspirin based on metabolic enzyme and PK-PD model. This clinical trial contain three groups, aspirin group, salvianolate injection group and combination (salvianolate injection+aspirin) group. Investigators collect blood samples at special time points during post-administration.Investigators have already find out the Salvianolate's pharmacokinetic characteristics in vivo and establish the biological sample-testing analysis method in previous research. Depending on these results, this clinical trial aim to explore the pharmacodynamics-pharmacokinetics(PK-PD) characteristics of combination with Salvianolate and aspirin through biomarkers, blood concentration. Finally clarify the TCM and WM material basis and mutual mechanism of drug interaction and guide reasonable clinical prescription.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meet the diagnostic criteria of coronary heart disease.
- •Meet the diagnostic criteria of stable angina pectoris.
- •Meet the diagnostic criteria of syndrome of blood stasis.
- •Angina in grade I-II according to Canadian cardiovascular society (CCS).
- •It could be enrolled if the subject taking aspirin or salvianolate injection with one month regularly。
- •The subjects were informed and voluntarily signed informed consent.
排除标准
- •Severe heart disease (acute myocardial infarction of acute myocardial infarction in 6 months), severe cardiopulmonary dysfunction (eg: cardiac function II)
- •Poorly controlled hypertension(systolic pressure >160mmHg or diastolic pressure >100mmHg).
- •Severe primary diseases such as liver and renal hematopoietic system damage. Such as:liver function（ALT≥2×ULN、AST≥2×ULN）,kidney function（Cr>1.0×ULN) or nervous and mental disorder.
- •Pregnant, breast-feeding and menstrual women, or women planning pregnancy within 3 months.
- •Subjects who participated in clinical trials in recent 3 months.
- •Subjects who took surgery treatment or had hemorrhagic tendency in recent 4 weeks.
- •Subjects who had drug allergy history or with allergic constitution.
- •Subjects who has mental or physical disorders.
- •Subjects who had bad compliance or is not suitable for this clinical trial by investigator's judgement
研究组 & 干预措施
aspirin arm
only take aspirin (100mg,qd) orally for 10 days treatment course
干预措施: Aspirin Tablet (Drug)
salvianolate injection arm
only inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course
干预措施: salvianolate injection (Drug)
aspirin and salvianolate injection arm
take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course
干预措施: salvianolate injection (Drug)
aspirin and salvianolate injection arm
take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course
干预措施: Aspirin Tablet (Drug)
结局指标
主要结局
Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.
时间窗: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Use flow cytometric method to detect the P-selection expression on platelet at different time points. Analyse the influence of Asprin/Salvianolate on platelet interaction adhesion during drug concentration-time curves.
Change of PAC-1 expression (platelet-associated complement) on the activated platelets at different time points.
时间窗: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Use flow cytometric method to detect the PAC-1 expression on platelet at different time points. Analyse the influence of Asprin/Salvianolate on platelet aggregation during drug concentration-time curves.
Change of P2Y12 acceptor expression on platelets at different time points. (P2Y12 acceptor is a receptor for ADP(adenosine diphosphate) and ATP (adenosine triphosphate )coupled to G-proteins that inhibit the adenylyl cyclase second messenger system)
时间窗: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Use flow cytometric method to detect the P2Y12 acceptor expression on platelet at different time points. Analyse the influence of Asprin/Salvianolate on platelets aggregation activated by ADP or ATP during drug concentration-time curves.
Change of PDE enzymes（phosphodiesterase）expression on platelet at different time points.
时间窗: Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h
Use ELISA method to detect the PDE enzymes expression at different time points. Analyse the influence of Asprin/Salvianolate on platelets activated by PDE enzymes during drug concentration-time curves.
次要结局
- Change of Aspirin esterase activity at different blood concentration of Asprin/Salvianolate(Getting blood sample before taking aspirin in day 8 and day 9.In the day 10, getting blood sample before taking aspirin and after taking aspirin in 5min、15min、30min、45min、1h、2h、4h、8h、12h、24h)
- Change of Catechol-o-methyltransferase (COMT) activity at different blood concentration of Asprin/Salvianolate(Getting blood sample before injection in day 8 and day 9.In the day 10, getting blood sample before injection and after injection in 5min、15min、30min、45min、1h、2h、4h、8h、12h、24h)