Abstract
For the following compounds: sulfamerazine, 4-hydroxysulfamerazine, N4acetylsulfamerazine, N4-acetyl4-hydroxysulfamerazine, the following data are reported: biosynthesis in the dog, isolation, identification by MS and NMR, TLC (Rf values) and HPLC (capacity factors and molar extinction), half-life of elimination, metabolism, renal excretion and protein binding in dog. Dogs are unable to acetylate sulfamerazine, but eliminate predominantly by hydroxylation of the N1-substituent. Administered N4-acetylsulfamerazine is predominantly eliminated by deacetylation to sulfamerazine which in turn is hydroxylated. The renal clearances of sulfamerazine and N4-acetylsulfamerazine in the dog are identical. The renal excretion of both compounds proceeds by the passive processes of glomerular filtration and tubular reabsorption.4-Hydroxysulfamerazine and its glucuronide have a higher renal clearance than sulfamerazine.
Similar content being viewed by others
References
Atef, M., andP. Nielsen (1975) Metabolism of sulphadiazine in cows.Xenobiotica 5, 167–172.
Bevill, R.F., R.M. Sharma, S.H. Meachum, S.C. Wozniak, D.W.A. Bourne andL.W. Dittert (1977) Disposition of sulfonamides in food-producing animals: Concentrations of sulfamethazine and its metabolites in plasma, urine, and tissues of lambs following intravenous administration.Am. J. Vet. Res. 38, 973–977.
Beyer, K.H., H.F. Russo, E.A. Patch, L. Peters andK.L.S. Glenolden (1946) The formation and excretion of acetylated sulfonamides.J. Lab. Clin. Med. 31, 65–71.
Bourne, D.W.A., R.F. Bevill, R.M. Sharma, R.P. Gural andL.W. Dittert (1977) Disposition of sulfonamides in food-producing animals: Pharmacokinetics of sulfamethazine in lambs.Am. J. Vet. Res. 38, 967–972.
Despopoulos, A. (1965) A definition of substrate specificity in renal transport of organic anions.J. Theor. Biol. 8, 163–192.
Earle, D.P. (1944) Renal excretion of sulfamerazine.J. Clin. Invest. 23, 914–920.
Fisher, S.L., L. Troat, A. Waterhouse andJ.A. Shannon (1943) The relation between chemical structure and physiological disposition of a series of substances allied to sulfanilamide.J. Pharmacol. Exp. Ther. 79, 373–391.
Hayashi, M., D.W.A. Bourne, R.F. Bevill andG.D. Koritz (1979) Disposition of sulfonamides in food-producing animals: pharmacokinetics of sulfamerazine in ewe lambs.Am. J. Vet. Res. 40, 1578–1582.
Hekster, Y.A., andT.B. Vree (1982) Clinical pharmacokinetics of sulphonamides and their N4-acetyl derivatives.Antibiot. Chemother. 31, 22–118.
Janssen, T.J., W.J.A. Wijnands, T.B. Vree, A.C.P. Van Den Dries, Y.A. Hekster, T.J.M. Campschreur andE.F.S. Termond (1983) Kinetiek en behandeling van drie overdoseringen met carbamazepine (Tegretol).J. Drug Res. 8, 1707–1717.
Loomis, T.A., R.S. Hubbard andG.F. Koepf (1943) The excretion of sulfanilamide and acetylsulfanilamide by the human kidney.Am. J. Physiol. 139, 197–207.
Nielsen, P. (1973) The metabolism of four sulphonamides in cows.Biochem. J. 136, 1039–1045.
Reinhold, J.G., H.F. Flippin, A.H. Domm, J.J. Zimmerman andL. Schwartz (1945) Renal clearance of sulfamerazine, sulfadiazine, sulfathiazole and sulfapyridine in man.J. Pharmacol. Exp. Ther. 83, 279–287.
Scudi, J.V. (1940) On the urinary excretion of ‘free’ sulfapyridine.Science 91, 486.
Scudi, J.V., andS.J. Childress (1956) Constitution of the hydroxysulfapyridine isolated from dog urine.J. Biol. Chem. 218, 587–593.
Sigel, C.W. (1983) Disposition and metabolism of trimethoprim, tetroxoprim, sulfamethoxazole and sulfadiazie. In:Inhibition of folate metabolism in chemotherapy (Hitchings, G.H., ed.). Berlin-Heidelberg-New York: Springer-Verlag, 163–185.
Ueda, M., K. Orita andT. Koizumi (1972) Studies on the metabolism of drugs. XIII. Quantitative separation of metabolites in human urine after oral administration of sulfisomezole and sulfaphenazole.Chem. Pharm. Bull. 20, 2047–2050.
Van Der Kleijn, E., T.B. Vree, A.M. Baars, R. Wijsman, L.C. Edmunds andH.J. Knop (1981) Factors influencing the activity and fate of benzodiazepines in the body.Br. J. Clin. Pharmaco., 11, 85S–98S.
Vree, T.B., Y.A. Hekster, J.E. Damsma, E. Van Der Kleijn andW.J. O'reilly (1979) Pharmacokinetics of N1-acetyland N4-acetylsulfamethoxazole in man.Clin. Pharmacokinet. 4, 310–319.
Vree, T.B., Y.A. Hekster, J.E. Damsma, M.W. Tijhuis andW.T. Friesen (1981) Pharmacokinetics and mechanism of renal excretion of short acting sulphonamides and N4-acetylsulphonamides in man. Structural requirements of sulphonamides for active tubular secretion.Eur. J. Clin. Pharmacol. 20, 283–292.
Vree, T.B., Y.A. Hekster, M.W. Tijhuis, M. Baakman, T.J. Janssen andE.F.S. Termond (1983a) The effects of the molecular structure of closely related N1-substituents of sulfonamides on the pathways of elimination of man.Pharm. Weekbl. [Sci.] 5, 49–56.
Vree, T.B., J.J. Reekers-Ketting, Y.A. Hekster andJ.F.M. Nouws (1983b) Acetylation and deacetylation of sulfonamides in dogs.J. Vet. Pharmacol. Ther. 6, 153–156.
Weber, C.J., J.J. Lalich andR.H. Major (1943) Metabolism of sulfapyridine in the dog.Proc. Soc. Exp. Biol. Med. 53, 190–192.
Woolley, J.L., A. Ragouzeous, D.A. Brent andC.W. Sigel (1980) Sulfonamide crystalluria: Isolation and identification of sulfamethoxazole and four metabolites in urinary calculi. In:Current chemotherapy and infectious disease (Nelson, J.D., andC. Grassi, eds.). Washington DC: The American Society for microbiology, 552–554.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vree, T.B., Tijhuis, M.W., Nouws, J.F.M. et al. Isolation and identification of 4-hydroxysulfamerazine and preliminary studies on its pharmacokinetics in dogs. Pharmaceutisch Weekblad Scientific Edition 6, 80–87 (1984). https://doi.org/10.1007/BF01953959
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01953959