Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1985 Dec;20(6):611–618. doi: 10.1111/j.1365-2125.1985.tb05119.x

Antipyrine metabolite kinetics in healthy human volunteers during multiple dosing of phenytoin and carbamazepine.

P N Shaw, J B Houston, M Rowland, K Hopkins, J F Thiercelin, P L Morselli
PMCID: PMC1400829  PMID: 4091993

Abstract

Antipyrine total clearance and the formation clearance of its major metabolites were studied in normal, healthy male volunteers before and after multiple dosing for approximately three weeks with phenytoin (six subjects) and carbamazepine (six subjects). Total antipyrine clearance increased on average by 91% after phenytoin dosing and by 61% after carbamazepine and individual increases correlated well with mean plasma concentrations of the anti-epileptic drug. The increase in total clearance resulted largely from increased formation clearances of the 4-hydroxy and 3-hydroxymethylantipyrine metabolites with minimal effect on the norantipyrine pathway, following treatment with both enzyme-inducing drugs. It is concluded that both phenytoin and carbamazepine have similar effects on antipyrine metabolism and that these effects are mediated by induction of specific forms of cytochrome P450.

Full text

PDF
611

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRODIE B. B., AXELROD J. The fate of antipyrine in man. J Pharmacol Exp Ther. 1950 Jan;98(1):97–104. [PubMed] [Google Scholar]
  2. Böttcher J., Bässmann H., Schüppel R. Quantitation and urinary pattern of 4,4'-dihydroxy-antipyrine, 4-hydroxy-antipyrine and 3-hydroxymethyl-antipyrine, as main metabolites of antipyrine in man and rat. J Pharm Pharmacol. 1982 Mar;34(3):168–175. doi: 10.1111/j.2042-7158.1982.tb04215.x. [DOI] [PubMed] [Google Scholar]
  3. Cunningham J. L., Evans D. A. Urinary D-glucaric acid excretion and acetanilide pharmacokinetics before and during diphenylhydantoin administration. Eur J Clin Pharmacol. 1974 Aug 23;7(5):387–391. doi: 10.1007/BF00558212. [DOI] [PubMed] [Google Scholar]
  4. Danhof M., Krom D. P., Breimer D. D. Studies on the different metabolic pathways of antipyrine in rats: influence of phenobarbital and 3-methylcholanthrene treatment. Xenobiotica. 1979 Nov;9(11):695–702. doi: 10.3109/00498257909042337. [DOI] [PubMed] [Google Scholar]
  5. Danhof M., Verbeek R. M., van Boxtel C. J., Boeijinga J. K., Breimer D. D. Differential effects of enzyme induction on antipyrine metabolite formation. Br J Clin Pharmacol. 1982 Mar;13(3):379–386. doi: 10.1111/j.1365-2125.1982.tb01389.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Danhof M., van Zuilen A., Boeijinga J. K., Breimer D. D. Studies of the different metabolic pathways of antipyrine in man. Oral versus i.v. administration and the influence of urinary collection time. Eur J Clin Pharmacol. 1982;21(5):433–441. doi: 10.1007/BF00542332. [DOI] [PubMed] [Google Scholar]
  7. Døssing M., Pilsgaard H., Rasmussen B., Poulsen H. E. Time course of phenobarbital and cimetidine mediated changes in hepatic drug metabolism. Eur J Clin Pharmacol. 1983;25(2):215–222. doi: 10.1007/BF00543794. [DOI] [PubMed] [Google Scholar]
  8. Eichelbaum M., Bertilsson L., Säwe J. Antipyrine metabolism in relation to polymorphic oxidations of sparteine and debrisoquine. Br J Clin Pharmacol. 1983 Mar;15(3):317–321. doi: 10.1111/j.1365-2125.1983.tb01505.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Petruch F., Schüppel R. V., Steinhilber G. Effect of diphenylhydantoin on hepatic drug hydroxylation. Eur J Clin Pharmacol. 1974 Jul 26;7(4):281–285. doi: 10.1007/BF00560345. [DOI] [PubMed] [Google Scholar]
  10. Pirttiaho H. I., Sotaniemi E. A., Pelkonen R. O., Pitkänen U. Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants. Eur J Clin Pharmacol. 1982;22(5):441–445. doi: 10.1007/BF00542550. [DOI] [PubMed] [Google Scholar]
  11. Rhodes J. C., Houston J. B. Antipyrine metabolite kinetics in phenobarbital and beta-naphthoflavone-induced rats. Drug Metab Dispos. 1983 Mar-Apr;11(2):131–136. [PubMed] [Google Scholar]
  12. Staiger C., Schlicht F., Walter E., Gundert-Remy U., Hildebrandt R., de Vries J., Wang N. S., Harenberg J., Weber E. Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol. Eur J Clin Pharmacol. 1983;25(6):797–801. doi: 10.1007/BF00542523. [DOI] [PubMed] [Google Scholar]
  13. Teunissen M. W., Joeres R. P., Vermeulen N. P., Breimer D. D. Influence of 9-hydroxyellipticine and 3-methylcholanthrene treatment on antipyrine metabolite formation in rats in vivo. Xenobiotica. 1983 Apr;13(4):223–231. doi: 10.3109/00498258309052258. [DOI] [PubMed] [Google Scholar]
  14. Teunissen M. W., Van Graft M., Vermeulen N. P., Breimer D. D. Influence of allylisopropylacetamide and phenobarbital treatment on in vivo antipyrine metabolite formation in rats. Xenobiotica. 1983 Aug;13(8):497–502. doi: 10.3109/00498258309052289. [DOI] [PubMed] [Google Scholar]
  15. Toverud E. L., Boobis A. R., Brodie M. J., Murray S., Bennett P. N., Whitmarsh V., Davies D. S. Differential induction of antipyrine metabolism by rifampicin. Eur J Clin Pharmacol. 1981;21(2):155–160. doi: 10.1007/BF00637517. [DOI] [PubMed] [Google Scholar]
  16. Vesell E. S. The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clin Pharmacol Ther. 1979 Sep;26(3):275–286. doi: 10.1002/cpt1979263275. [DOI] [PubMed] [Google Scholar]
  17. Yoshimura H., Shimeno H., Tsukamoto H. Metabolism of drugs. LIX. A new metabolite of antipyrine. Biochem Pharmacol. 1968 Aug;17(8):1511–1516. doi: 10.1016/0006-2952(68)90210-4. [DOI] [PubMed] [Google Scholar]
  18. van Boxtel C. J., Wilson J. T., Lindgren S., Sjöqvist F. Comparison of the half-life of antipyrine in plasma, whole blood and saliva of man. Eur J Clin Pharmacol. 1976 Feb 6;9(4):327–332. doi: 10.1007/BF00561668. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES