Eva-Luise Hobl, PhD, from the Medical University of Vienna, and colleagues conducted a randomized, double-blind, placebo-controlled, cross-over trial in which 24 healthy subjects were given a loading dose of 600mg clopidogrel along with placebo or 5mg morphine intravenously. Liquid chromatography tandem mass spectrometry was used to determine pharmacokinetics. Platelet function tests measured clopidogrel effects.
The researchers found that morphine significantly delayed clopidogrel resorption (P=0.025) and reduced the area under the curve levels of its active metabolite by 52% (P=0.001). Two hours was the average delay in maximal inhibition of platelet aggregation with morphine (24 patients; P>0.001). For one to four hours after morphine injection, residual platelet aggregation was higher (24 patients; P>0.005). Morphine also delayed platelet plug formation inhibition under high shear rates (21 patients; P>0.004). In extensive and rapid metabolizers, morphine abolished the three-fold prolongation in collagen adenosine diphosphate induced closure times (16 patients; P=0.001).
“Morphine delays clopidogrel resorption, decreases plasma levels of clopidogrel active metabolite, retards and diminishes its effects, which can lead to treatment failure in susceptible individuals,” Hobl and colleagues conclude.