Crushed clopidogrel administered via nasogastric tube has faster and greater absorption than oral whole tablets

Abstract

Objectives: To compare the absorption of 300 mg clopidogrel administered crushed via nasogastric (NG) tube versus whole tablets taken orally in healthy volunteers.

Background: Earlier antiplatelet therapy has proven benefits in treatment of myocardial infarction and in patients undergoing PCI. Aspirin can be delivered early in crushed form via NG tube after CABG surgery to prevent graft occlusion. If clopidogrel given crushed via NG tube provides faster absorption, it could allow earlier clopidogrel loading.

Methods: Nine healthy human subjects (34.7 +/- 11.1 years, 5 males) were given 300 mg clopidogrel in crushed form via NG tube with 30 mL water after 8 hours of fasting. Plasma levels of the primary circulating inactive clopidogrel metabolite SR26334 were measured after 20 minutes, 40 minutes, 1, 2, 4, 8, 12, and 24 hours of dosing. Following >or=2 week washout, same subjects swallowed 300 mg clopidogrel (four 75 mg tablets) after an 8-hour fasting and SR26334 levels were measured at the same time points.

Results: Plasma SR26334 concentrations peaked earlier after crushed delivery than after oral intake (44 vs. 70 minutes, P = 0.023) and the median peak was 80% higher (13,083 vs. 7,255 ng/mL, respectively, P = 0.021). At 40 minutes, area under the curve was almost twofold greater with NG administration than oral administration (geometric means ratio = 0.5299, 95% CI = 0.28-0.99, P = 0.048), but was similar over the 24-hour period with both administration methods (geometric means ratio = 1.05, 95% CI = 0.84-1.32, P = 0.646).

Conclusions: A 300 mg loading dose of crushed clopidogrel administered via NG tube provides faster and greater bioavailability than an equal dose taken orally as whole tablets. The clinical benefits of this strategy need to be investigated.