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Pharmacological properties of five diclofenac metabolites identified in human plasma

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Abstract

Five metabolites of diclofenac sodium (Voltarol®) have been identified in human plasma. All five metabolites were more than 50 times less potent than diclofenac in inhibiting PGE2 production in zymosan-stimulated mouse macrophages and LTC4 synthesis was not inhibited in these cells. Anti-inflammatory activity (adjuvant arthritis and carragheenan-induced paw oedema in rats) and analgesic activity (phenyl-p-benzoquinone writhing, mouse) of the metabolites were at least 10 times lower when compared to diclofenac. There was a good correlation betweenin vitro PGE2 inhibition andin vivo activities for diclofenac and its metabolites indicating that inhibition of prostaglandin synthesis is a major mechanism responsible for their pharmacological actions.

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References

  1. A. P. Todd and E. M. Sorkin,Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs35, 244–285 (1988).

    PubMed  Google Scholar 

  2. H. Stierlin, J. W. Faigle, A. Sallmann, W. Kueng, J. W. Richter, H.-P. Kriemler, K. O. Alt and T. Winkler,Biotransformation of diclofenac sodium (Voltaren ®)in animals and in man. I. Isolation and identification of principal metabolites. Xenobiotica9, 601–610 (1979).

    PubMed  Google Scholar 

  3. H. Stierlin and J. W. Faigle,Biotransformation of diclofenac sodium (Voltaren ®)in animals and man. II. Quantitative determination of the unchanged drug and principal phenolic metabolites, in urine and bile. Xenobiotica9, 611–621 (1979).

    PubMed  Google Scholar 

  4. P. H. Degen, W. Dieterle, W. Schneider, W. Theobald and U. Sinterhauf,Pharmacokinetics of diclofenac and five metabolites after single doses in healthy volunteers and after repeated doses in patients. Xenobiotica18, 1449–1455 (1988).

    PubMed  Google Scholar 

  5. J. W. Faigle, I. Boettcher, J. Godbillon, H. P. Kriemler, E. Schlumpf, W. Schneider, A. Schweizer, H. Stierlin and T. Winkler,A new metabolite of diclofenac sodium in human plasma, Xenobiotica18, 1191–1197 (1988).

    PubMed  Google Scholar 

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

    Google Scholar 

  7. I. Wiesenberg-Boettcher, A. Schweizer, J. R. Green, K. Mueller, F. Maerki and J. Pfeilschifter,The pharmacological profile of CGP 28238, a novel highly potent anti-inflammatory compound. Drugs Expl. Clin. Res.XV, 501–509 (1989).

    Google Scholar 

  8. A. Schweizer, R. Brom and H. Scherrer,Combined automated writhing/motility test for testing analgesics. Agents and Actions23, 29–31 (1988).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., R-1056.P. 07, Basel, Switzerland

    I. Wiesenberg-Boettcher, J. Pfeilschifter, A. Schweizer, A. Sallmann & P. Wenk

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  1. I. Wiesenberg-Boettcher
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  2. J. Pfeilschifter
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  3. A. Schweizer
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  4. A. Sallmann
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  5. P. Wenk
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Wiesenberg-Boettcher, I., Pfeilschifter, J., Schweizer, A. et al. Pharmacological properties of five diclofenac metabolites identified in human plasma. Agents and Actions 34, 135–137 (1991). https://doi.org/10.1007/BF01993259

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