title: Can N-acetylcysteine reverse the antiplatelet effects of clopidogrel? An in vivo and vitro study.
abstract: BACKGROUND
  The active metabolite of clopidogrel binds the P2Y12 ADP receptor on the platelet surface via a disulfide bond. N-Acetylcysteine (NAC) is able to reduce disulfide bonds. We postulated that NAC might reverse clopidogrel's effect on platelets.
  
  
  METHODS
  Two groups of patients were investigated. Group 1 included 11 patients with stable coronary disease who, after discontinuation of aspirin, received 14 days of clopidogrel, 75 mg/day. Bleeding time and whole-blood platelet aggregometry (with 5 micromol/L ADP) were compared before and after the 14 days. Patients were then treated with 6 g of NAC orally, followed by repeat measurement of bleeding time and aggregometry. In group 2, 14 patients were treated with clopidogrel (300 mg) and aspirin before a percutaneous coronary intervention. Blood was drawn 22 +/- 3 hours later and divided into 2 samples. One was sent immediately for platelet-rich plasma aggregometry (using 5 and 2 micromol/L ADP, collagen, and arachidonic acid as agonists), thromboelastography, and aggregometry using the Plateletworks assay (Helena Laboratories, Beaumont, Tex). The other sample was treated with NAC (500 mg/L), after which these same platelet function tests were performed.
  
  
  RESULTS
  In group 1, NAC therapy did not significantly change the bleeding time or results of aggregometry. In group 2, neither aggregometry nor the Plateletworks assay suggested reversal of inhibition by NAC.
  
  
  CONCLUSIONS
  These studies reveal that a large dose of NAC does not reduce inhibition of platelet aggregation by clopidogrel in vitro or in vivo.
authors.affiliation: Department of Cardiology, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, TX, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Campbell
authors.forename: Peter B
authors.initials: PB
authors.lastname: Berger
authors.forename: Greg A
authors.initials: GA
authors.lastname: Nuttall
authors.forename: James L
authors.initials: JL
authors.lastname: Orford
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Santrach
authors.forename: William C
authors.initials: WC
authors.lastname: Oliver
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ereth
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Thompson
authors.forename: M Katie
authors.initials: MK
authors.lastname: Murphy
authors.forename: David L
authors.initials: DL
authors.lastname: McGlassen
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Schrader
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000077144:Clopidogrel; D004347:Drug Interactions; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D000111:Acetylcysteine