September 22, 2010Open Access
Ver artículo completoPharmacodynamic Effects of Concomitant Versus Staggered Clopidogrel and Omeprazole Intake
Resultado clave
Staggering omeprazole and clopidogrel administration did not significantly differ from concomitant administration in P2Y12 reactivity index at 1 week (61.6% vs 56.1%; P=0.08).
Diseño del estudio
Tipo
RCT (n=20)
Enmascaramiento
Open-label
Aleatorización
crossover
PICO estructurado
Does staggered administration of omeprazole and clopidogrel improve platelet inhibition compared to concomitant administration in healthy volunteers?
P
Población
20 healthy volunteers treated with clopidogrel and omeprazole in a 3-period randomized crossover design.
I
Intervención
Omeprazole 40 mg daily staggered by 8 to 12 hours from clopidogrel (600-mg loading dose followed by 75-mg maintenance dose) for 1 week
C
Comparador
Omeprazole 40 mg daily concomitantly with clopidogrel, and clopidogrel alone
O
Resultado
P2Y12 reactivity index assessed by vasodilator-stimulated phosphoprotein phosphorylation assay at 1 weeksurrogate
Omeprazole impairs clopidogrel-induced antiplatelet effects during the maintenance phase regardless of whether the doses are staggered or administered concomitantly.
Resultado numérico
Tasa de eventos absoluta: 56.1% vs 61.6%
valor p: p=0.08
Resumen
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. Methods and 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.