Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study.
BACKGROUND
A drug interaction between clopidogrel and omeprazole resulting in impaired platelet inhibition has been reported. It has been suggested that staggering administration of clopidogrel and omeprazole may overcome this pharmacodynamic (PD) interaction.


RESULTS
This prospective, open-label, 3-period, randomized crossover study was performed in 20 healthy volunteers. Subjects were randomly selected to receive omeprazole (40 mg daily) concomitantly (CONC) or staggered by 8 to 12 hours (STAG) for 1 week on a background of clopidogrel therapy in a crossover fashion, with a 2- to 4-week washout period between treatments. After another 2- to 4-week washout period, all subjects were treated for 1 week with clopidogrel alone. Clopidogrel was administered as a 600-mg loading dose followed by a 75-mg maintenance dose during all phases. PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, VerifyNow P2Y(12) system, and light transmittance aggregometry at baseline, 24 hours, and 1 week. The primary end point was the comparison of P2Y(12) reactivity index assessed by vasodilator-stimulated phosphoprotein phosphorylation assay at 1 week between CONC and STAG regimens. No significant difference in the primary end point was observed (least squares mean ± SEM, 56.1 ± 3.5% for CONC versus 61.6 ± 3.4% for STAG; P = 0.08). P2Y(12) reactivity index values were significantly lower in the clopidogrel regimen (48.8 ±3.4%) than in the CONC (P = 0.02) and STAG (P = 0.001) regimens. No PD differences were observed between regimens at baseline and 24 hours. Concordant results were obtained by P2Y(12)-specific assessments using VerifyNow but not with light transmittance aggregometry.


CONCLUSIONS
Omeprazole impairs clopidogrel-induced antiplatelet effects in the maintenance phase of treatment irrespective of timing of their administration.
Ferreiro
José L
JL
University of Florida College of Medicine-Jacksonville, Jacksonville, FL 32209, USA.
Ueno
Masafumi
M
Capodanno
Davide
D
Desai
Bhaloo
B
Dharmashankar
Kodlipet
K
Darlington
Andrew
A
Charlton
Ronald K
RK
Bass
Theodore A
TA
Angiolillo
Dominick J
DJ
D000328:Adult; D002985:Clinical Protocols; D000077144:Clopidogrel; D004344:Drug Incompatibility; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine