Abstract
Sulfadiazine, sulfamerazine, sulfadimidine and their corresponding N4-acetyl derivatives were administered to man. The percentages of acetylation and deacetylation, protein binding, half-lives of elimination and apparent and true renal clearance values were measured. Methyl substitution in the N1-pyrimidine ring favours acetylation by an additional N-acetyltransferase isoenzyme present in ‘fast’ acetylators only. Methyl substitution in the N1-pyrimidine ring favours renal clearance of the N4-acetylsulfonamide derivatives. The N1-substituent probably reinforces the binding of the N4-acetyl group to the active tubular transport mechanism. The renal clearance of these sulfonamides is not dependent on the structure of the N1-substituent.
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Bell, Ph., andR.O. Roblin (1942)J. Am. Chem. Soc. 64, 2905–2917.
Evans, D.A.P., andT.A. White (1964)J. Lab. Clin. Med. 63, 394–403.
Frisk, A.R. (1943)Acta Med. Scand. 142, suppl CXIII, 1–199.
Hearse, D.J., andW.W. Weber (1973)Biochem. J. 132, 519–526.
Hekster, Y.A., andT.B. Vree (1982)Antibiot. Chemother. 31, 22–188.
Krebs, H.A., W.O. Sykes andW.C. Bartley (1947)Biochem. J. 41, 622–630.
Krüger-Thiemer, E., andP. Bünger (1965)Proc. Eur. Soc. Study Drug Tox. 6, 185–207.
Lehr, D. (1957)Ann. NY Acad. Sci. 69, 417–447.
Metzler, C.M., G.L. Elfring andA.J. Mcewen (1974)Biometrics (September), 562–575.
Northey, E.H. (1940)Chem. Rev. 27, 85–197.
Portwich, F., andH. Büttner (1956)Arch. Exp. Pathol. Pharmacol. 229, 513–519.
Rieder, J. (1963)Arzneimittelforsch. 13, part I, 81–88; part II, 89–93; part III, 93–103.
Seydel, J.K. (1965) In:Physico-Chemical Aspects of Drug Action (Ariëns, E.J., Ed.). Pergamon Press, Oxford - London, 169–180;Ibidem (1968)J. Pharm. Sci. 57, 1455–1478.
Struller, Th. (1968) In:Progress in Drug Research no. 12 (Jucker, E., Ed.). Birkhäuser Verlag, Basel - Stuttgart: 389–452.
Talseth, T., andK.H. Landmark (1977)Eur. J. Clin. Pharmacol. 11, 33–36.
Vree, T.B., Y.A. Hekster, A.M. Baars, J.E. Damsma andE. Van Der Kleijn (1978)Clin. Pharmacokin. 3, 319–329.
Vree, T.B., Y.A. Hekster, J.E. Damsma, E. Van Der Kleijn andW.J. O'reilly (1979)Clin. Pharmacokin. 4, 310–319;Ibidem (1980)Clin. Pharmacokin. 5, 274–294.
Vree, T.B., Y.A. Hekster, J.E. Damsma, M. Tijhuis andW.T. Friesen (1981)Eur. J. Clin. Pharmacol. 20, 283–293.
Vree, T.B., Y.A. Hekster, M. Baakman, A.M. Baars, T.J. Janssen, M.O. Oosterbaan, E. Termond andM.W. Tijhuis (1982) In:Current Chemotherapy and Immunotherapy. Proc. 12th Int. Congress of Chemotherapy, Florence 1981. The American Society for Microbiology, Washington, 140–142.
Vree, T.B., M.W. Tijhuis, M. Baakman andY.A. Hekster (1983)Biomed. Mass Spec. 10, 114–119.
Weber, W.W., andS.N. Cohen (1968)Biochem. Biophys. Acta 151, 276–278.
Weber, W.W., H.E. Radtke andR.H. Tannen (1980) In:Extrahepatic metabolism of drugs and other foreign compounds (Gram, T.E., Ed.). MTP Press, Lancaster, UK, 493–531.
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Vree, T.B., Hekster, Y.A., Tijhuis, M.W. et al. The effect of the molecular structure of closely related N1-substituents of sulfonamides on the pathways of elimination in man. Pharmaceutisch Weekblad Scientific Edition 5, 49–56 (1983). https://doi.org/10.1007/BF01960075
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DOI: https://doi.org/10.1007/BF01960075