Antiplatelet effect of acetylsalicylic acid, metamizole and their combination - in vitro and in vivo comparisons.
BACKGROUND
Acetylsalicylic acid (ASA) plays an important role in the treatment and prevention of cardiovascular diseases. Metamizole (MET) is an analgesic and antipyretic medicine, it is not used as an antiplatelet drug.


OBJECTIVE
We aimed to examine the antiplatelet effect of MET and the possible interactions between the drugs.


METHODS
In our in vitro investigations different concentrations of ASA and MET solutions were added to blood. To examine the interactions MET and ASA were added together. In our in vivo crossover study intravenous MET, oral ASA or both drugs together were administered. Epinephrine and adenosine-diphosphate induced platelet aggregation was determined by optical aggregometry.


RESULTS
Epinephrine-induced aggregation was completely inhibited in all ASA and MET concentrations in vitro. Lower, ineffective concentration of MET prevented the antiplatelet effect of ASA. The inhibition was completely restored when higher concentration of ASA was used or when ASA was added first. Our in vivo study showed that in the MET group rapid onset of inhibition was developed and there was no inhibition after one day. In the ASA group platelet aggregation decreased slowly but still had significant inhibitory effect after 72 hours. Combined therapy showed similar changes to the MET group.


CONCLUSIONS
Antiplatelet effect of MET and ASA did not differ significantly in vitro. The observations may indicate a competitive interaction between the two drugs. The in vivo experiments showed that intravenously administered MET is an effective antiplatelet drug and can be considered as a therapeutic alternative, when ASA cannot be used in oral form.
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
J
J
Papp
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
B
B
Sandor
Department of Pathophysiology and Gerontology, School of Medicine, University of Pecs, Pecs, Hungary Hungarian National Ambulance Service, Pecs, Hungary.
Z
Z
Vamos
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
D
D
Botor
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
A
A
Toth
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
M
M
Rabai
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
P
P
Kenyeres
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary Hungarian National Ambulance Service, Pecs, Hungary.
P
P
Cseplo
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
I
I
Juricskay
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
E
E
Mezosi
Department of Pathophysiology and Gerontology, School of Medicine, University of Pecs, Pecs, Hungary.
A
A
Koller
1st Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
K
K
Toth
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D018592:Cross-Over Studies; D004177:Dipyrone / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D004177:Dipyrone; D001241:Aspirin; D004837:Epinephrine