Journal of Clinical & Experimental Pathology
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Primary Topic Other:
Pharmacogenomics testing continues to gain foothold in clinical practice. CYP2C19 genotyping to predict
responsiveness to clopidogrel, emerging markers for hepatitis C therapy and combinatorial CYP450 genotyping for psychotropics
are some examples. Wider translation of these new pharmacogenomic tests would have a major impact on efficacy and safety.
Physicians, Pathologists, Lab Directors, Clinical Chemists, Technologists, IVD Industry Scientists, and Clinical
Increasingly, there are new and emerging pharmacogenomic markers for personalizing drug therapies in
cardiology, infectious diseases and psychiatry. In 2010, the FDA issued a ?black box? warning regarding the use of clopidogrel
in patients who are poor metabolizers for cytochrome P450 2C19, the principal enzyme involved in converting clopidogrel
to the active drug. Clopidogrel inhibits platelet aggregation and is used to treat patients with cardiac disease, especially after
percutaneous coronary intervention. Retrospective studies have shown that patients who are slow or intermediate metabolizers
have a higher rate of adverse outcomes after stent placement than patients who are wild-type for CYP 2C19. In addition to the
role of genotyping for assessing the pharmacokinetic effect, measurement of platelet function is important for assessing the
pharmacodynamic effect of clopidogrel. There may also be a role for direct measurement of the active clopidogrel metabolite.
Clopidogrel is scheduled to go off patent in 2012, which will widen the gap of drug costs between it and new anti-platelet
medications such as prasugrel. Hepatitis C virus infects 170 million people worldwide, and can lead to permanent liver damage
and cancer. Interferon alpha plus ribavirin is the standard treatment, effective in 80% of patients with genotype 2 or 3, and 50%
effective for type 1b. Dual therapy has severe side effects often requiring dose modification or discontinuation. Recently, GWAS
have identified that SNPs near IL28B are strongly associated with outcome of combination therapy. Protective IL28B SNPs are
strongly associated with on-treatment viral kinetics and approximately 2-fold increased sustained viral response rates in HCV
genotype 1 and 4. New therapies based on protease inhibitors are expected to be soon available and may be used as a triple
drug therapy, requiring new pharmacogenomic studies. Psychotropics are metabolized by multiple CYP450 pathways, each of
which, in isolation may inadequately account for a drug?s pharmacokinetic properties. Emerging research points to the value
of a combinatorial approach that considers CYP2C9, CYP2C19 and CYP2D6 as integrative components of a hepatic enzyme
system for drug metabolism. This could be employed for patient-specific selection of psychotropics optimized to the innate drug
metabolism reserve of each individual. This proposed symposium will explain how integration of clinical and genetic data may
be needed for personalizing drug therapy.
After this this session, participants will be able to: 1)Understand the potential impacts of pharmacogenomics
in the personalized drug therapies of common diseases; 2)Explain the need for pharmacogenomic testing for clopidogrel, Hep C
drugs and psychotropics; 3)Identify commercial technologies for these pharmacogenomic testing.
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