title: Obesity and Inflammation and Altered Clopidogrel Pharmacokinetics and Pharmacodynamics.
abstract: Clopidogrel is a key antiplatelet drug that has substantial interpatient variability in pharmacodynamic response. Patients with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk of cardiovascular events. Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy. Central to the obesity-related risk of atherothrombosis is a pro-thrombotic state characterized by increased levels of coagulation factors, impaired fibrinolysis and platelet hyper-reactivity, which results from the interaction among the features clustering in obesity: insulin resistance, inflammation, oxidative stress, and endothelial dysfunction.
  
  
  
  A number of reports have demonstrated that obesity is a risk factor for a reduced clopidogrel pharmacodynamic response. The inflammatory state associated with obesity, particularly a metabolic endotoxemia, may set in motion, a number of mechanisms that increase platelet reactivity, suppress cytochrome P450 enzyme activity, and increase platelet turnover, all contributing to a poor clopidogrel response.
  
  
  
  Comprehensive understanding of the mechanisms underlying obesity-related high onclopidogrel platelet reactivity will help in the optimization of antithrombotic therapy in this patient population.
authors.affiliation: Department of Internal Medicine University of Missouri Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO. United States.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Norgard
authors.affiliation: Department of Pharmacy Practice, Clinical Assistant Professor, University at Buffalo School of Pharmacy & Pharmaceutical Sciences, Buffalo, NY. United States.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Monte
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism / Q000517:prevention & control; D000077144:Clopidogrel; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Obesity; clopidogrel; endotoxin; inflammation; platelet function.; thienopyridine metabolism