Isolation and identification of 4-hydroxysulfamerazine and preliminary studies on its pharmacokinetics in dogs
- 38 Downloads
- 29 Citations
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.
Keywords
Public Health Internal Medicine Glomerular Filtration Renal Clearance Renal ExcretionPreview
Unable to display preview. Download preview PDF.
References
- Atef, M., andP. Nielsen (1975) Metabolism of sulphadiazine in cows.Xenobiotica 5, 167–172.PubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- Despopoulos, A. (1965) A definition of substrate specificity in renal transport of organic anions.J. Theor. Biol. 8, 163–192.CrossRefPubMedGoogle Scholar
- Earle, D.P. (1944) Renal excretion of sulfamerazine.J. Clin. Invest. 23, 914–920.Google Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- Hekster, Y.A., andT.B. Vree (1982) Clinical pharmacokinetics of sulphonamides and their N4-acetyl derivatives.Antibiot. Chemother. 31, 22–118.PubMedGoogle Scholar
- 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.Google Scholar
- 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.Google Scholar
- Nielsen, P. (1973) The metabolism of four sulphonamides in cows.Biochem. J. 136, 1039–1045.PubMedGoogle Scholar
- 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.Google Scholar
- Scudi, J.V. (1940) On the urinary excretion of ‘free’ sulfapyridine.Science 91, 486.Google Scholar
- Scudi, J.V., andS.J. Childress (1956) Constitution of the hydroxysulfapyridine isolated from dog urine.J. Biol. Chem. 218, 587–593.PubMedGoogle Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- Weber, C.J., J.J. Lalich andR.H. Major (1943) Metabolism of sulfapyridine in the dog.Proc. Soc. Exp. Biol. Med. 53, 190–192.Google Scholar
- 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.Google Scholar