Display options
Share it on
Full text links
Wiley Free PMC Article

Br J Clin Pharmacol. 1982 Mar;13(3):379-86. doi: 10.1111/j.1365-2125.1982.tb01389.x.

Differential effects of enzyme induction on antipyrine metabolite formation.

British journal of clinical pharmacology

M Danhof, R M Verbeek, C J van Boxtel, J K Boeijinga, D D Breimer

PMID: 7059438 PMCID: PMC1402128 DOI: 10.1111/j.1365-2125.1982.tb01389.x
Free PMC Article

Abstract

1 The influence of enzyme induction with antipyrine and pentobarbitone was studied on the rates of formation of the major metabolites of antipyrine: 4-hydroxyantipyrine, norantipyrine and 3-hydroxymethyl-antipyrine + 3-carboxy-antipyrine. The inducing drugs were given to panels of healthy volunteers for 8 days and prior to and after this period antipyrine total elimination clearance was determined in plasma, whereas the partial clearances for production of the individual metabolites were assessed on the basis of urinary excretion data. 2 Antipyrine total clearance had significantly increased by 16% following treatment with antipyrine, which could almost entirely be attributed to a selective increase in the rate of production of norantipyrine. 3 With pentobarbitone total clearance of antipyrine had increased by 60%, which was associated with a significant increase in the clearance of production of all three metabolites. However, the increase in norantipyrine formation was significantly higher than the increase in 4-hydroxyantipyrine and 3-hydroxymethyl-antipyrine formation. 4 The most likely explanation for these differences in the degree of induction of the different metabolic routes of antipyrine, is that different enzymes are involved in the different routes. Apparently the enzyme involved in norantipyrine formation is most sensitive to induction by antipyrine and pentobarbitone. By measuring rates of antipyrine metabolite formation it may be possible to study the degree of selectivity of enzyme inducers on oxidative drug metabolism.

References

  1. Pharmacol Rev. 1967 Sep;19(3):317-66 - PubMed
  2. Biochem Pharmacol. 1968 Aug;17(8):1511-6 - PubMed
  3. J Clin Invest. 1969 Dec;48(12):2202-9 - PubMed
  4. Chem Pharm Bull (Tokyo). 1971 Jan;19(1):41-5 - PubMed
  5. Clin Sci. 1971 Apr;40(4):351-64 - PubMed
  6. J Pharm Pharmacol. 1973 Jan;25(1):83-4 - PubMed
  7. Pharmacology. 1973;10(6):338-44 - PubMed
  8. Clin Sci Mol Med. 1974 Apr;46(4):511-8 - PubMed
  9. Pharmacology. 1975;13(2):112-27 - PubMed
  10. Eur J Clin Pharmacol. 1975 Dec 19;9(2-3):219-27 - PubMed
  11. Br J Clin Pharmacol. 1976 Oct;3(5):907-13 - PubMed
  12. Toxicol Appl Pharmacol. 1977 Jan;39(1):97-104 - PubMed
  13. Clin Pharmacol Ther. 1977 Apr;21(4):470-81 - PubMed
  14. Clin Pharmacol Ther. 1977 Sep;22(3):316-21 - PubMed
  15. Clin Pharmacol Ther. 1977 Sep;22(3):336-9 - PubMed
  16. Arzneimittelforschung. 1978;28(2):315-9 - PubMed
  17. J Pharmacokinet Biopharm. 1978 Feb;6(1):7-39 - PubMed
  18. Lancet. 1979 Feb 10;1(8111):300-2 - PubMed
  19. Clin Pharmacol Ther. 1979 Apr;25(4):423-7 - PubMed
  20. Clin Pharmacol Ther. 1979 May;25(5 Pt 1):591-7 - PubMed
  21. Eur J Clin Pharmacol. 1979 Mar 26;15(2):139-45 - PubMed
  22. Clin Pharmacol Ther. 1979 Sep;26(3):326-9 - PubMed
  23. Drug Metab Rev. 1979;9(2):221-36 - PubMed
  24. Br J Clin Pharmacol. 1979 Dec;8(6):529-37 - PubMed
  25. Pharmacology. 1979;19(4):215-20 - PubMed
  26. Xenobiotica. 1979 Nov;9(11):695-702 - PubMed
  27. J Pharmacol Exp Ther. 1950 Jan;98(1):97-104 - PubMed

Substances

MeSH terms

Publication Types

LinkOut - more resources