Genetic CYP2C19 polymorphism dependent non-responders to clopidogrel therapy--does structural design, dosing and induction strategies have a role to play?
Recent evidences suggest that genetic CYP2C19 polymorphism plays a role in the development of treatment resistance for clopidogrel's antiplatelet therapy. This short communication puts forward some strategies that could be potentially used to overcome the genetic polymorphism associated hurdles. While there is some established evidence for an induction strategy and design of chemical structure, the proposed dosing input strategy is speculative in nature. Such thought process and novel explorations are important for delivering medicines in genetically and ethnically diverse populations.
Srinivas
Nuggehally R
NR
Suramus Biopharm, Integrated Drug Development, J.P. Nagar I phase, Bangalore 560 025, India.
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D015195:Drug Design; D004351:Drug Resistance; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine