Postgraduation Registration Detail

Research Registry No : PRID-00870_V2
Registration Date : 2020-07-23
Thesis Title : Effect of CYP2C19*2 Polymorphism on the activity of Clopidogrel in Healthy Volunteers
Author Name : Phyu Phyu Thwin
City : Yangon
State/ Region : Yangon
Field of Thesis : Clinical Pharmacy
Education Status : B.Pharm., M. Pharm., Ph. D. (Clinical Pharmacy)
Host Department Address : Department of Pharmacology
Supervisor's Name : Prof. Dr. Latt Latt Win
Supervisor's Designation : Professor and Head
Supervisor’s Home Department :
Year of Post Graduation : 2019
Name and Placement of University : University of Pharmacy
Academic Level : Ph.D/Doctorate
Thesis Notes for Specialty : PhD Thesis (Clinical Pharmacy)
Abstract : Genetic polymorphism can alter the pharmacokinetics and pharmacodynamics responses of drugs and change in therapeutic outcomes and strongly impact Adverse Drug Reactions. Clopidogrel is an antiplatelet agent, used alone, or in combination with aspirin in patients with ischaemic heart disease. It is prodrug and requires to convert to active thiol metabolite by metabolic enzyme CYP2C19 in liver. The aim of this study was to study the effect of CYP2C19*2 genetic polymorphism on the activity of Clopidogrel in healthy participants. The objectives were to determine the frequency of CYP2C19*1/*1 (wild) and CYP2C19*1/*2 (heterozygous) genotypes among healthy participants and to compare the effect of P2Y12 receptor blockade (platelet reactivity index-PRI) by Clopidogrel in the above two genotypes. The study design was laboratory-based analytical study. In phase I, 76 participants, either sex, were recruited for determination of CYP2C19 genotypes. The genotypes of extracted DNA were identified by PCR-RFLP method. Among 76 healthy participants, 39 (51.31%) were normal/wild type (*1/*1), 36 (47.36%) were heterozygous (*1/*2) and 1 (1.31%) was homozygous (*2/*2) genotype for CYP2C19*2 gene. In phase II, whole blood PRI after Clopidogrel was compared between twelve participants each with wild (*1/*1) genotype and heterozygous (*1/*2) genotype. One tablet (75 mg) of Clopidogrel, with meal, was given to each participant daily for 14 days. Whole blood PRI of Clopidogrel was determined by using ELISA method on day 0, day 3, day 7, day 10, and day 14. The changes of mean PRI of participants with heterozygous and wild genotype within the study periods were (87.93% and 86.91%; p=0.71) on day 0, (62.51% and 58.55%; p=0.64) on day 3, (43.13% and 27.85%; p=0.07) on day 7, (46.80% and 21.83%; p=0.01) on day 10 and (49.12% and 26.93%; p=0.01) on day 14, two hours after oral administration of Clopidogrel. The antiplatelet activity of Clopidogrel in heterozygous type was significantly reduced (p<0.05) on day 10 and 14. Therefore, the Clopidogrel-treated heterozygous genotype group is at high risk for experiencing adverse cardiovascular events.\r\n\r\nKey words: CYP2C19*2 Polymorphism, Clopidogrel, Platelet Reactivity Index (PRI), \r\n enzyme-linked immunosorbent assay (ELISA)
IRB/PRC/ERC Approval Date : 2017-01-31
Placement of IRB/PRC/ERC : University of Pharmacy, Yangon
IRB/PRC/ERC Approval Letter/PRC/Document : 23072020040857CertificateofEthics.pdf
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