Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction.
Delays in the onset of action of prasugrel during primary percutaneous coronary intervention (PPCI) have been reported and could be related to the effects of morphine on gastric emptying and subsequent intestinal absorption. The study objective was to determine whether morphine delays the onset of action of prasugrel in patients with a prior history of ST-elevation myocardial infarction (STEMI) treated with PPCI. This was a crossover study of 11 aspirin-treated patients with prior history of STEMI treated with PPCI, for which prasugrel and morphine had been previously administered. Patients were randomised to receive either morphine (5 mg) or saline intravenously followed by 60 mg prasugrel. Blood samples were collected before randomised treatment and over 24 hours after prasugrel administration. The inhibitory effects of prasugrel on platelets were determined using the VerifyNow P2Y12 assay and light transmission aggregometry. Plasma levels of prasugrel and prasugrel active metabolite were measured. Platelet reactivity determined by VerifyNow PRU, VerifyNow % Inhibition and LTA was significantly higher at 30-120 minutes (min) when morphine had been co-administered compared to when saline had been co-administered. Morphine, compared to saline, significantly delayed adequate platelet inhibition after prasugrel administration (158 vs 68 min; p = 0.006). Patients with delayed onset of platelet inhibition also had evidence of delayed absorption of prasugrel. In conclusion, prior administration of intravenous morphine significantly delays the onset of action of prasugrel. Intravenous drugs may be necessary to reduce the risk of acute stent thrombosis in morphine-treated STEMI patients undergoing PPCI.
Mark R
MR
Thomas
Allison C
AC
Morton
Rashed
R
Hossain
Beining
B
Chen
Lei
L
Luo
Nur Nazihah B Md
NN
Shahari
Peng
P
Hua
Richard G
RG
Beniston
Heather M
HM
Judge
Prof. Robert F. Storey, MD, DM, FESC, Department of Cardiovascular Science, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK, Tel.: +44 114 3052004, Fax: +44 114 2711863, E-mail r.f.storey@sheffield.ac.uk.
Robert F
RF
Storey
D000368:Aged; D018592:Cross-Over Studies; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects*; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000072657:ST Elevation Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D013997:Time Factors
D010975:Platelet Aggregation Inhibitors; D009020:Morphine; D000068799:Prasugrel Hydrochloride
P2Y12 inhibitors; Prasugrel; antiplatelet medications; morphine; platelet reactivity