Premium
Aspirin Decreases Systemic Exposure to Clopidogrel Through Modulation of P‐Glycoprotein But Does Not Alter Its Antithrombotic Activity
Author(s) -
Oh J,
Shin D,
Lim K S,
Lee S,
Jung KH,
Chu K,
Hong K S,
Shin KH,
Cho JY,
Yoon S H,
Ji S C,
Yu KS,
Lee H,
Jang IJ
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2014.49
Subject(s) - clopidogrel , aspirin , pharmacology , antithrombotic , pharmacokinetics , bioavailability , active metabolite , medicine , pharmacodynamics , cyp2c19 , oral administration , platelet aggregation inhibitor , metabolism , cytochrome p450
Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P‐gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75‐mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once‐daily 100‐mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined. The P‐gp microRNA miR‐27a increased by up to 7.67‐fold ( P = 0.004) and the clopidogrel area under the concentration–time curve (AUC) decreased by 14% ( P > 0.05), but the AUC of H4 remained unchanged and RPI increased by up to 15% ( P = 0.002) after aspirin administration. These findings indicate low‐dose aspirin coadministration may decrease clopidogrel bioavailability but does not decrease its efficacy. Clinical Pharmacology & Therapeutics (2014); 95 6, 608–616. doi: 10.1038/clpt.2014.49