Skip to main content
Log in

Interaction of diclofenac and ketoprofen with cardioactive drugs in rats

  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Summary

The interaction of diclofenac and ketoprofen, both applied intraperitoneally in a dose of 8 mg/kg for twenty-eight days, was assessed with cardioactive drugs in rats. Interaction was assessed on the basis of ECG records after the infusion of adrenaline, verapamil or lidocaine to the rats treated with diclofenac or ketoprofen vs control. The infusion time was measured in seconds to the moment of the appearance of the first heart reaction to the infusion of the cardioactive drug, then to the appearance of more frequent changes in the ECG record, and finally, to the occurrence of the toxic effect. It was also measured the plasma concentrations of sodium and potassium ions. As well as diclofenac and ketoprofen concentration, 2 hours after single and 28th dose. ECG patterns revealed no occurrence of cardiotoxic action of diclofenac and ketoprofen. The treatment with diclofenac caused significantly lower sodium plasma concentrations whereas the concentration of potassium was increased. Diclofenac concentrations were the same after a single and multiple doses, whereas concentrations of ketoprofen were significantly higher after a single dose than after its multiple applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. McGettigan P., Henry D. (2006): Cardiovascular risik and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxigenase 2. JAMA, 296, 1633–1634.

    Article  PubMed  CAS  Google Scholar 

  2. Ray W.A., Stein C.M., Hall K. (2002): Daugherty J.R., Griffin M.R. Non steroidal anti-inflammatory drugs and risk of serious coronary heart disease; an observational cohort. Lancet, 359, 118–123.

    Article  PubMed  CAS  Google Scholar 

  3. Andersohn F. (2006): Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs and risk of acute myocardial infarction. Circulation, 113, 1950–1957.

    Article  PubMed  CAS  Google Scholar 

  4. Motola D., Vaccheri A., Silvani M.C., Poluzzi E., Bottoni A., De Ponti F., Montanaro N. (2004): Pattern of NSAID use in the Italian general population: a questionnaire-based survey. Eur. J. Clin. Pharmacol., 60, 731–738.

    Article  PubMed  Google Scholar 

  5. Jick H., Kaye J.A., Russmann S., Jick S.S (2006): Nonsteroidal antiimflammatory drugs and acute myocardial infarction in patients with no major risk factors. Pharmacotherapy, 26, 1379–1387.

    Article  PubMed  CAS  Google Scholar 

  6. EMEA press release on non-selective NSAIDS. August 2nd, 2005,http://www.emea.eu.int/pdfs/humanlpress/pr/24732305en. pdf Accessed 23 August 2006.

  7. Arun P.R., Azeez P.A. (2004): Vulture population decline, diclofenac and avian gout. Cun. Sci., 87, 565–568.

    CAS  Google Scholar 

  8. Singh G., Wu 0., Ranghorne P., Madhok R. (2006): Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis. Arthritis Res. Ther., 8, 153–158.

    Article  CAS  Google Scholar 

  9. Jakovljevic V., Stanulovic M., Sabo A., Popovic M.(1989): Effect of chronic consumption of caffeine on the autonomous system of isolated rat heart. Yugoslav. Physiol. Pharmacol. Acta, 25,51–53.

    Google Scholar 

  10. Jakovljevic V., Sabo A., Popovic M., Stanulovic M. (1990): Interaction between methaixantine and cardioactive drugs. (Abstract). Eur. J. Pharmacol., 183.

  11. Vasovic V., Vukmirovic S., Poša M., Mikov M., Raškovic A., Jakovljevic V. (2006): Effect of rat pretreatment with aqueous solution of stevioside and bile acids on the action of certain cardioactive drugs. Eur. J. Drug Metabol. Pharmacokinet., 31, 311–314.

    Article  CAS  Google Scholar 

  12. Turner R.A.: Screening Methods in Pharmacology, Academic Press, New York and London, 1965.

    Google Scholar 

  13. Owen S.G., Michael S.R., William T.F. (1987): Rapid High-performance liquid chromatographic assay for the simultaneus analysis of non-steroidal antiinflamatory drugs in plasma. J. Chromatogr., 416, 293–302.

    Article  PubMed  CAS  Google Scholar 

  14. USP. The United States Pharmacopeia. The national formulary. USP 26th revision (January 1, 2003). NF 21st ed (Januar 1, 2003). Rockville, MD: The United States Pharmacopoeia Convention, Inc., 2002.

    Google Scholar 

  15. Clasco R.K., Ed.: USP DI Drug information for the Health Care P professional. Thomson MICROMEDEX, Inc 2003 P. IV/3 17

  16. Johnston S.A., Fox S.M. (1997): Mechanism of action of anti-inflammatory medications used for the treatment of osteoarthritis. J. Am. Veterin. Med. Assoc., 210, 1486–1492.

    CAS  Google Scholar 

  17. Oaks J.L., Gilbert M., Virani M.Z., Watson R.T., Meteyer C.U., Rideout B.A., Shivaprasad H.L., Ahmed S., Chaudhry M.J., Arshad M., Mahmood S., Au A., Khan A.A (2004): Diclofenac residues as the cause of vulture population decline in Pakistan. Nature, 427, 630–633.

    Article  PubMed  CAS  Google Scholar 

  18. Noory T., Jarrar B.M. (2006): Histochemical Alterations in the Spleen of Rabbits Induced by Diclofenac Sodium (Voltaren). Science, 19, 21–29.

    Google Scholar 

  19. Masubuchi Y., Nakayama S., Hone T. (2002): Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats. Hepatology, 35, 544–551.

    Article  PubMed  CAS  Google Scholar 

  20. Hunter R.P., Isaza R., Koch D.E. (2003): Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus). Am. J. Veterin. Res., 64, 109–114.

    Article  CAS  Google Scholar 

  21. Ishizaki T., Sasaki T., Suganuma T., Horai Y., Chiba K., Watanabe M., Asuke W., Hoshi H. (1980): Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral. Eur. J. Clin. Pharmacol., 18, 407–414.

    Article  PubMed  CAS  Google Scholar 

  22. Aberg G., Ciofalo V.B., Pendleton R.G., et al. (1995): Inversion of (R)- to (S)-ketoprofen in eight animal species. Chirality, 7, 383–387.

    Article  PubMed  CAS  Google Scholar 

  23. Lees P., Taylor P.M., Landoni F.M., Arifah A.K., Waters C. (2003): Ketoprofen in the Cat. Pharmacodyn. Chiral Pharmacokinet. Veterin. J. 165, 21–35.

    Article  CAS  Google Scholar 

  24. McGettigan P., Henry D. (2006): Cardiovascular risik and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxigenase 2. JAMA, 296, 1633–1634.

    Article  PubMed  CAS  Google Scholar 

  25. Ray W.A., Stein C.M., Hall K. (2002): Daugherty J.R., Griffin M.R. Non steroidal anti-inflammatory drugs and risk of serious coronary heart disease; an observational cohort. Lancet, 359, 118–123.

    Article  PubMed  CAS  Google Scholar 

  26. Andersohn F. (2006): Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs and risk of acute myocardial infarction. Circulation, 113, 1950–1957.

    Article  PubMed  CAS  Google Scholar 

  27. Motola D., Vaccheri A., Silvani M.C., Poluzzi E., Bottoni A., De Ponti F., Montanaro N. (2004): Pattern of NSAID use in the Italian general population: a questionnaire-based survey. Eur. J. Clin. Pharmacol., 60, 731–738.

    Article  PubMed  Google Scholar 

  28. Jick H., Kaye J.A., Russmann S., Jick S.S (2006): Nonsteroidal antiimflammatory drugs and acute myocardial infarction in patients with no major risk factors. Pharmacotherapy, 26, 1379–1387.

    Article  PubMed  CAS  Google Scholar 

  29. EMEA press release on non-selective NSAIDS. August 2nd,2005) http://www.emea.eu.intlpdfs/humanlpress/pr/24732305en.pd f Accessed 23 August 2006.

  30. Arun P.R., Azeez P.A. (2004): Vulture population decline, diclofenac and avian gout. Curr. Sci., 87, 565–568.

    CAS  Google Scholar 

  31. Singh G., Wu O., Ranghorne P., Madhok R. (2006) Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis. Arthritis Res. Ther., 8, 153–158.

    Article  CAS  Google Scholar 

  32. Jakovljevic V., Stanulovic M., Sabo A., Popovic M.(l989): Effect of chronic consumption of caffeine on the autonomous system of isolated rat heart. Yugoslav. Physiol. Pharmacol. Acta, 25, 51–53. 33. Jakovljevic V., Sabo A., Popovic M., Stanulovic M. (1990): Interaction between methalxantine and cardioactive drugs. (Abstract). Eur. J. Pharmacol., 183.

    Google Scholar 

  33. Vasovic V., Vukmirovic S., Poša M., Mikov M., Raškovic A., Jakovljevic V. (2006): Effect of rat pretreatment with aqueous solution of stevioside and bile acids on the action of certain cardioactive drugs. Eur. J. Drug Metabol. Pharmacokinet., 31,311–314.

    Article  CAS  Google Scholar 

  34. Turner R.A.: Screening Methods in Pharmacology, Academic Press, New York and London, 1965.

    Google Scholar 

  35. Owen S.G., Michael S.R., William T.F. (1987): Rapid High-performance liquid chromatographic assay for the simultaneus analysis of non-steroidal antiinflamatory drugs in plasma. J. Chromatogr., 416, 293–302.

    Article  PubMed  CAS  Google Scholar 

  36. USP. The United States Pharmacopeia. The national formulary. USP 26th revision (January 1, 2003). NF 2lst ed (January 1, 2003). Rockville, MD: The United States Pharmacopoeia Convention, Inc., 2002.

    Google Scholar 

  37. Clasco R.K., Ed.: USP DI Drug information for the Health Care P professional. Thomson MICROMEDEX, Inc 2003 P. IV/317

  38. Johnston S.A., Fox S.M. (1997): Mechanism of action of anti-inflammatory medications used for the treatment of osteoarthritis. J. Am. Veterin. Med. Assoc., 210, 1486–1492.

    CAS  Google Scholar 

  39. Oaks J.L., Gilbert M., Virani M.Z., Watson R.T., Meteyer C.U., Rideout B.A., Shivaprasad H.L., Ahmed S., Chaudhry M.J., Arshad M., Mahmood S., Ali A., Khan A.A (2004): Diclofenac residues as the cause of vulture population decline in Pakistan. Nature, 427, 630–633.

    Article  PubMed  CAS  Google Scholar 

  40. Noory T., Jarrar B.M.(2006): Histochemical Alterations in the Spleen of Rabbits Induced by Diclofenac Sodium (Voltaren). Science, 19, 21–29.

    Google Scholar 

  41. Masubuchi Y., Nakayama S., Hone T. (2002): Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats. Hepatology, 35, 544–551.

    Article  PubMed  CAS  Google Scholar 

  42. Hunter R.P., Isaza, R., Koch D.E. (2003): Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus). Am. J. Veterin. Res., 64, 109–114.

    Article  CAS  Google Scholar 

  43. Ishizaki T., Sasaki T., Suganuma T., Horai Y., Chiba K., Watanabe M., Asuke W., Hoshi H. (1980): Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral. Eur. J. Clin. Pharmacol., 18, 407–414.

    Article  PubMed  CAS  Google Scholar 

  44. Aberg G., Ciofalo V.B, Pendleton R.G., et al. (1995): Inversion of (R)- to (S)-ketoprofen in eight animal species. Chirality, 7, 383–387.

    Article  PubMed  CAS  Google Scholar 

  45. Lees P., Taylor P.M., Landoni F.M., Arifah A.K., Waters C. (2003): Ketoprofen in the Cat: Pharmacodyn. Chiral Pharmacokinet. Veterin. J. 165, 21–35.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jakovljevic, V., Sabo, A., Tomić, Z. et al. Interaction of diclofenac and ketoprofen with cardioactive drugs in rats. Eur. J. Drug Metabol. Pharmacokinet. 34, 11–17 (2009). https://doi.org/10.1007/BF03191378

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03191378

Key words

Navigation