Sandor LifeSciences
Biosciences Research Services

Pharmacogenomics

What is pharmacogenomics?

  • Application of genomic information to predict safety and efficacy of medication.
  • Out-of 3 billion Nucleotides base pair (bp) of human genome, 3 million SNP’s are well characterized variation in a single nucleotide, which contributing to inter-individual variation.
  • Such variation was observed in genes regulating pharmacokinetics (absorption, distribution, metabolism and elimination) and pharmacodynamic (Drug target) pathways, thus influence response to therapy.
  • Using genetic algorithms, mathematical models and artificial neural network, the genetic information can be used to provide personalized suitability on the type and the dose of the drugs.
  • It would prevent hundreds of thousands of deaths annually due to drug adverse reactions.

Cardiology Panel

Warfarin

Nature of Drug :

  • Oral anti-coagulant

Indications :

  • Valve replacement therapy, Aortic fibrillation,deep vein thrombosis.

Clinical challenge :

  • High interindividual variability in dose requirement(1-10 mg).
  • Nano therapeutic range: International Normalized Ratio (INR) should be maintain between(2.0-3.5)

Adverse Drug Reaction :

  • INR >2 - intravascular coagulation.
  • INR >3.5 - Bleeding.

Pharmacokinetics :

Pharmacodynamics :

Pharmaco Genomics Testing :

  • Five functional polymorphisms in PK and PD pathways of Warfarin will be detected using PCR followed by Sanger Sequencing.
  • A well established pharmacogenomics algorithm will guide in initiating the Warfarin dose

Benefits :

  • The therapeutic INR can be attained at a faster rate.
  • Risk for adverse drug reactions significantly decreases.
  • Minimizes hospitalization duration.

Sample Required :

  • EDTA blood 3-4ml.
  • Can be transported at 4°C.

Clopidogrel

Nature of Drug:

  • Platelet ADP receptor inhibitor

Indications:

  • Myocardial infractions (reduces the risk of stroke or heart attack)
  • Do not uses Clopidogrel if you have allergy, active bleeding, while using Proton pump inhibitors like Omeprazole, Esomeprazole

Adverse Drugs Reactions:

  • Dizziness, risk for Results for thrombotic thrombocytopenic purpura (pale skin, purple skin patches, hemolytic anemia, stomach or back pain)

Pharmacogenomics Testing:

  • Clopidogrel is a prodrug which is acted upon by CYP2C19 to form active drug

The CYP2C19 activity will decide the safety and efficacy

  • Poor metabolizer Phenotype: Drug will remain as prodrug with no efficacy.
  • Intermediate metabolizer: Drug is safe and effective.
  • Ultra rapid metabolizer: All the drug is converted to active form, thus impairing even normal platelet function

Dose Recommendations:

  • As per the Clinical Pharmacogenetic implementation consortium guide lines

Will be updated

Nephrology Panel

Nature of Drug :

  • Macrolide based immune suppressant.

Indications :

  • Renal and liver transplant, glomerular kidney disease, psoriasis.

Adverse Drug Reactions:

  • Cancer, anemia, diabetes mellitus, cardiomyopathy, hepatitis, Myasthenia gravis (MG).

Pharmacokinetics:

  • Tacrolimus requires low expression of phospho glycoprotein (PGP)/Multidrug resistance protein 1 (MDR1) to have better option across the intestine.
  • It is metabolized by CYP3A4 and CYP3A5 in the liver.

Pharmacodynamics:

  • Tacrolimus inhibits FKBP protein thus interfering with calcineurin pathway.
  • It inhibits activation of T-Lymphocytes and cytokine production.

Pharmacogenomic Testing:

  • The four functional polymorphisms in pharmacokinetic pathway of Tacrolimus will determined the bioavailability of the drug.
  • It inhibits activation of T-Lymphocytes and cytokine production.
  • PCR followed by Sanger sequencing will be used to detect these SNP’s (single nucleotide polymorphisms).
  • Tacrolimus dose titration can be performed based on pharmacogenomics algorithm.

Will be updated

Will be updated

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