Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo-oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers.


METHODS
Ten healthy male volunteers were given ketoprofen 1.4 mg x kg(-1), ketorolac 0.4 mg x kg(-1) and diclofenac 1.1 mg x kg(-1) in saline i.v. on three different occasions, at more than one-week intervals, in a randomized double-blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion.


RESULTS
Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 microg x m[-1]) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (P<0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 microg x ml[-1]) induced platelet aggregation was still seen (26.7%) (P<0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 microM and 6 microM) induced platelet aggregation and ketoprofen in ADP (6 microM) induced platelet aggregation in sample 2. Bleeding time was prolonged (P<0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs.


CONCLUSIONS
Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.
Niemi
T T
TT
Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
Taxell
C
C
Rosenberg
P H
PH
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004008:Diclofenac / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D007660:Ketoprofen / Q000494:pharmacology*; D020910:Ketorolac; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D004008:Diclofenac; D007660:Ketoprofen; D014046:Tolmetin; D020910:Ketorolac