Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2014, vol. 23, nr 3, May-June, p. 377–380

Publication type: original article

Language: English

Effect of Ketoprofen on Lactic Dehydrogenase from Human Platelets

Muhammad Tahir Razi1,A,E, Ibrahim Javed1,C,D, Muhammad Zabta Choudry2,F, Muhammad Tariq Khan1,B, Noreen Mukhtar1,B

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan

2 Multan Medical & dental college, Multan, Pakistan


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.
Conclusion. 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.

Key words

ketoprofen, thrombocytopenia, lactic dehydrogenase, enzyme inhibition, pyruvate, kinetics.

References (24)

  1. Hochholzer W, Trenk D, Bestehorn HP, Fischer B, Valina CM, Ferenc M, Gick M, Caputo A, Büttner HJ, Neumann FJ: Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J am coll cardiol 2006, 48, 1742–1750.
  2. Meyer S: Platelet inhibition in clinical practice. Therapeutische Umschau. Revue thérapeutique 2012, 69, 631–633.
  3. Fink J, Gu F, Vasudevan SG: Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever. Rev Med Virol 2006, 16, 263–275.
  4. Kuter DJ: New thrombopoietic growth factors. blood 2007, 109, 4607–4616.
  5. Nikanne E, Kokki H, Salo J, Linna TJ: celecoxib and ketoprofen for pain management during tonsillectomy: a placebo-controlled clinical trial. Otolaryngolog Head Neck 2005, 132, 287–294.
  6. Luba M, Gusarski I: Thrombocytopenia as a complication of nonsteroidal anti-inflammatory drug treatment. Przeglad lekarski 2005, 62, 1556–1557.
  7. Jauhari A, Bista D, Johorey A, Saha S, Saha A: Thrombocytopenia after ibuprofen: a case report. J clin diagn Res 2009, 3, 1329–1333.
  8. Chernyak N, Sventsitskaya M, Guseinov CS: energy metabolism of platelets. b exp biol Med 1960, 49, 251–253.
  9. Doery JCG, Hirsh J, Cooper I: energy metabolism in human platelets: interrelationship between glycolysis and oxidative metabolism. blood 1970, 36, 159–168.
  10. Wróblewski F, Ladue JS: Lactic dehydrogenase activity in blood. Proc Soc exp biol Med 1955, 90, 210–213.
  11. Farabegoli F, Vettraino M, Manerba M, Fiume L, Roberti M, Stefano GD: Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways. eur J Pharm Sci 2012, 47, 729–738.
  12. O’Brien J, Kla KM, Hopkins IB, Malecki EA, McKenna MC: Kinetic parameters and lactate dehydrogenase isozyme activities support possible lactate utilization by neurons. Neurochem Res 2007, 32, 597–607.
  13. Kakkar T, Boxenbaum H, Mayersohn M: estimation of K i in a competitive enzyme-inhibition model: comparisons among three methods of data analysis. drug Metab dispos 1999, 27, 756–762.
  14. Kim EJ, Lim KM, Kim KY, Bae ON, Noh JY, Chung SM, Shin S, Yun YP, Chung JH: doxorubicin-induced platelet cytotoxicity: a new contributory factor for doxorubicin-mediated thrombocytopenia. J Thrombos Haemost 2009, 7, 1172–1183.
  15. Altman R, Honig S, Levin J, Lightfoot R: Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. The Journal of Rheumatology 1988, 15, 1422–1426.
  16. Hanna M, Elliott K, Stuart-Taylor M, Roberts D, Buggy D, Arthurs G: comparative study of analgesic efficacy and morphine-sparing effect of intramuscular dexketoprofen trometamol with ketoprofen or placebo after major orthopaedic surgery. b J clin Pharmacol 2003, 55, 126–133.
  17. Franck H, Rau R, Herborn G: Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate. clin Rheumatol 1996, 15, 163–167.
  18. Ishizaki T, Sasaki T, Suganuma T, Horai Y, Chiba K, Watanabe M, Asuke W, Hoshi H: Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration. eur J cli Pharmacol 1980, 5, 407–414.
  19. Rençber S, Karavana Sy, Özyazici M: bioavailability file: KeTOPROfeN. fabad J Pharm Sci 2009, 34, 203–216.
  20. Upton R, Williams R, Guentert T, Buskin J, Riegelman S: Ketoprofen pharmacokinetics and bioavailability based on an improved sensitive and specific assay. eur J clin Pharmacol 1981, 2, 127–133.
  21. Zabala S, Calpe M, Pérez G, Lerín F, Mouronval L: Neutropenia, thrombocytopenia and hepatic injury associated with dexketoprofen trometamol therapy in a previously healthy 35-year-old woman. J clin Pharm Ther 2008, 33, 79–81.
  22. Keluskar P, Ingle S: ethnopharmacology guided screening of traditional Indian herbs for selective inhibition of Plasmodium specific Lactate dehydrogenase. J ethnopharmacol 2012, 144, 201–207.
  23. Kim SR, Lee JY, Lee MY, Chung SM, Bae ON, Chung JH: association of quinone-induced platelet anti-aggregation with cytotoxicity. Toxicol Sci 2001, 62, 176–182.
  24. Cameron A, Read J, Tranter R, Winter VJ, Sessions RB, Brady RL, Vivas L, Easton A, Kendrick H, Croft SL: Identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity. J biol chem 2004, 279, 31429–31439.