title: Effect of ketoprofen on lactic dehydrogenase from human platelets.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan.
authors: Muhammad Tahir
authors: MT
authors: Razi
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan.
authors: Ibrahim
authors: I
authors: Javed
authors: Multan Medical & Dental College, Multan, Pakistan.
authors: Muhammad Zabta
authors: MZ
authors: Choudry
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan.
authors: Muhammad Tariq
authors: MT
authors: Khan
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan.
authors: Noreen
authors: N
authors: Mukhtar
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006801:Humans; D007660:Ketoprofen / Q000633:toxicity*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D019289:Pyruvic Acid / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D009243:NAD; D019289:Pyruvic Acid; D007660:Ketoprofen; D007770:L-Lactate Dehydrogenase