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Effect of ketoprofen on lactic dehydrogenase from human platelets.

BACKGROUND
In different clinical investigations of thrombocytopenia, ketoprofen was found to be the associated cause. Ketoprofen alone or in combination with other therapeutic regimens leads to a decrease in platelet count. Thrombocytopenia due to ketoprofen use can be a threatening condition to the patients who require uncompromised platelet function.


OBJECTIVES
In order to establish a mechanism for thrombocytopenia associated with ketoprofen use, the enzyme inhibition effects of ketoprofen on lactic dehydrogenase (LDH) were investigated in this study. LDH is essentially involved in platelet energy production.


MATERIAL AND METHODS
LDH isolated from human platelets was subjected to different concentrations of ketoprofen (250, 500, 750, 1000 and 1500 µg/mL) and pyruvate as a substrate (45, 60 and 90 µM/mL) to gain insight into the enzyme inhibition effects for forward reaction. Oxidation of nicotinamide adenine dinucleotide (NADH) was measured at 340 nm to evaluate enzyme activity. Enzyme inhibition kinetics were studied via Lineweaver Burk plot.


RESULTS
Ketoprofen was found to be a competitive inhibitor of LDH in human platelets. 89% of enzyme activity was inhibited by a 1500 µg/mL concentration of the drug and the enzyme inhibition constant was 882 µg/mL.


CONCLUSIONS
The possible main cause of thrombocytopenia due to ketoprofen use is LDH inhibition in platelets, which are essential for platelet energy metabolism. So patients who require uncompromised platelet function and are receiving ketoprofen in their prescription should be monitored for platelet count and blood clotting.