The pharmacokinetics of diclofenac sodium following intravenous and oral administration

Summary

The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 µg · ml−1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Boxenbaum, H. G., Riegelman, S., Elashoff, R.: Statistical estimations in pharmacokinetics. J. Pharmacokinet. Biopharm.2, 123–48 (1974)

    Google Scholar 

  2. 2.

    Geiger, U. P., Degen, P. H., Sioufli, A.: Quantitative assay of diclofenac in biological material by gas-liquid chromatography. J. Chromatogr.111, 293–298 (1975)

    Google Scholar 

  3. 3.

    Gibaldi, M., Perrier, D.: Pharmacokinetics. Vol. 1. Drugs and the pharmaceutical sciences. New York: Marcel Dekker 1975

    Google Scholar 

  4. 4.

    Kendall, M. J., Thornhill, D. P., Willis, J. V.: Factors affecting the pharmacokinetics of diclofenac sodium. Rheumatol. Rehabil. (in press)

  5. 5.

    Krupp, P. J., Exer, B., Menassé, R., Ziel, R.: Neue Aspekte der Entzündungshemmung durch nicht-steroide Antiphlogistika: Wirkung von Voltaren. Schweiz. Med. Wochenschr.105, 646 (1975)

    Google Scholar 

  6. 6.

    Krupp, P. J., Menassé-Gdynia, R., Sallmann, A., Wilhelmi, G., Ziel, R., Jaques, R.: Sodium (0-((2,6-dichlorophenyl)-amino)-phenyl)-acetate (GP 45,840) a new non-steroidal anti-inflammatory agent. Experientia29, 450 (1978)

    Google Scholar 

  7. 7.

    Kornguth, M. L., Monson, R. A., and Kunin, C. M.: The binding of antibiotics to a soluble protein from rat liver. J. Infect. Dis.129, 552–558 (1974)

    Google Scholar 

  8. 8.

    Kornguth, M. L., Monson, R. A., and Kunin, C. M.: The binding of penicillin antibiotics to a human liver protein. Arch. Biochem. Biophys.174, 339–343 (1976)

    Google Scholar 

  9. 9.

    Menassé, R., Hedwall, P. R., Kraetz, J., Pericin, C., Riesterer, L., Sallmann, A., Ziel, R., Jaques, R.: Pharmacological properties of diclofenac sodium and its metabolites. Scand. J. Rheumatol. Suppl.22, 5–16 (1978)

    Google Scholar 

  10. 10.

    Metzler, C. M.: A user's manual for NONLIN Technical Report 7292/69/7292/005, Upjohn Company, Kalamazoo, MI, November 25, 1969

  11. 11.

    Riess, W., Stierlin, H., Faigle, J. W., Geiger, U. P., Gerardin, A., Schmid, K., Sulc, M., Wagner, J., Theobald, W. P.: Kinetik und Biotransformation von Diclofenac in Tier und Mensch. Therapiewoche26, 18 (1976)

    Google Scholar 

  12. 12.

    Riess, W., Stierlin, H., Degen, P., Faigle, J. W., Gerardin, A., Moppert, J., Sallmann, A., Schmid, K., Schweizer, A., Sulc, M., Theobald, W., Wagner, J.: Pharmacokinetics and metabolism of the anti-inflammatory agent Voltaren. Scand. J. Rheumatol. Suppl.22, 17–29 (1978)

    Google Scholar 

  13. 13.

    Stierlin, H., Faigle, J. W. and Columbi, A.: Pharmacokinetics of diclofenac sodium (Voltaren) and metabolites in patients with impaired renal function. Scand. J. Rheumatol. Suppl.22, 30–35 (1978)

    Google Scholar 

  14. 14.

    Wagner, J. G.: Do you need a pharmacokinetic model, and if so, which one? J. Pharmacokinet. Biopharm.3, 457–478 (1955)

    Google Scholar 

  15. 15.

    Willis, J. V., Kendall, M. J.: Pharmacokinetic studies on diclofenac sodium in young and old volunteers. Scand. J. Rheumatol. Suppl.22, 36–41 (1978)

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Willis, J.V., Kendall, M.J., Flinn, R.M. et al. The pharmacokinetics of diclofenac sodium following intravenous and oral administration. Eur J Clin Pharmacol 16, 405–410 (1979). https://doi.org/10.1007/BF00568201

Download citation

Key words

  • diclofenac
  • plasma levels
  • intravenous bolus administration
  • oral administration
  • enteric coating
  • bioavailability