Mechanism of Drug-drug Interaction Between Salvianolate Injection and Aspirin

NCT03306550 | Unknown

• 1 other identifier: zz0908022
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Angina, Stable

Keywords

drug-drug interaction; Asprin; salvianolate injection; PK-PD model; metabolic enzymes

Outcome Measures

Primary Outcomes (4)

• Change of P-selection expression(platelet activation-dependent granule membrane) at different time points.

  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.

  Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

• Change of PAC-1 expression (platelet-associated complement) on the activated platelets at different time points.

  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.

  Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

• 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)

  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.

  Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

• Change of PDE enzymes（phosphodiesterase）expression on platelet at different time points.

  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.

  Getting blood sample before taking medicine in the day 10 and after it in 15min、1h、2h、8h、24h

Secondary Outcomes (2)

• 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

Study Arms (3)

aspirin arm

ACTIVE COMPARATOR

only take aspirin (100mg,qd) orally for 10 days treatment course

Drug: Aspirin Tablet

salvianolate injection arm

ACTIVE COMPARATOR

only inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course

Drug: salvianolate injection

aspirin and salvianolate injection arm

EXPERIMENTAL

take aspirin (100mg,qd) orally and inject salvianolate(200mg+5%Glucose Injection 250ml，iv) for 10 days treatment course

Drug: salvianolate injection; Drug: Aspirin Tablet

Interventions

salvianolate injection DRUG

The main ingredient of salvianolate injection is salvianolic acid B(SAB) which is extracted from the root of red salvia. Red salvia is used in traditional Chinese Medicine. It could promote blood circulation to removing blood stasis,which is clinically effective in treatment for cardiovascular disease.

aspirin and salvianolate injection arm; salvianolate injection arm

Aspirin Tablet DRUG

Anti-platelet medicine treatment and Chinese traditional medicine (TCM) promoting blood circulation to removing blood stasis is widely used in treatment for cardiovascular disease.

aspirin and salvianolate injection arm; aspirin arm

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Diabetics.
• 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

Sponsors & Collaborators

• Xiyuan Hospital of China Academy of Chinese Medical Sciences: lead

Related Publications (2)

• Cao W, Yang Q, Zhang W, Xu Y, Wang S, Wu Y, Zhao Y, Guo Z, Li R, Gao R. Drug-drug interactions between salvianolate injection and aspirin based on their metabolic enzymes. Biomed Pharmacother. 2021 Mar;135:111203. doi: 10.1016/j.biopha.2020.111203. Epub 2021 Jan 3.

  PMID: 33401223 DERIVED

• Zhang W, Zhu B, Cao W, Li R, Wang S, Gao R. Research on the mechanism of drug-drug interaction between salvianolate injection and aspirin based on the metabolic enzyme and PK-PD model: study protocol for a PK-PD trial. Trials. 2018 Sep 14;19(1):491. doi: 10.1186/s13063-018-2861-7.

  PMID: 30217228 DERIVED

MeSH Terms

Conditions

Angina, Stable

Interventions

salvianolate; Aspirin

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Rui Li, MD,Phd

CONTACT

0086+01062835651; crystal005@163.com

wantong Zhang, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2017
• First Posted: October 11, 2017
• Study Start: October 10, 2017
• Primary Completion: April 10, 2018
• Study Completion: October 10, 2018
• Last Updated: October 11, 2017

Record last verified: 2017-08