Metabolism and Pharmacokinetics of Sulfamonomethoxine in Edible Fish Species

  • Ryuji Ueno


Sulfamonomethoxine has been efficacious in the treatment of various bacterial diseases of fish. The present paper reviews recent studies on the metabolism and pharmacokinetics of sulfamonomethoxine in edible fish species such as yellowtail, rainbow trout, and eel. N4-Acetylated metabolites were the major metabolites whereas glucuronic acid conjugates were the minor metabolites. Moreover, a double conjugated metabolite, the glucuronic acid conjugate of N4-acetylsulfamonomethoxine was found in three species. Serum concentrations after intravascular administration could be fitted to be a two-compartment model and those after oral administration to a one-compartment model in all three species. The absorption parameters of sulfamonomethoxine in eel were substantially different from those in rainbow trout and yellowtail. In eel, the drug was assimilated slowly and cleared very slowly. On the other hand, in yellowtail, sulfamonomethoxine was well distributed to the tissues and was cleared quickly. As an application of the pharmacokinetic studies, the Japanese dosage regimens of sulfa-monomethoxine in three fish species were evaluated.


Rainbow Trout Channel Catfish Withdrawal Period Acetylator Phenotype Oxolinic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baggot, J.D., Ludden, T.M., and Powers, T.E., 1976, The bioavailability, disposition kinetics and dosage of sulphadimethoxine in dogs, Can. J Comp. Med., 40:310.PubMedGoogle Scholar
  2. Barron, M.G., Gedutis, C., and James, O.M., 1988, Pharmacokinetics of sulphadimethoxine in the lobster, Hamarus americanus, following intrapericardial administration, Xenobiotica, 18:269.PubMedCrossRefGoogle Scholar
  3. Bratton, A.C., and Marshall, E.K., 1939, A new coupling component of sulfanilamide determination, J. Biol. Chem.,128:537.Google Scholar
  4. Carli, S., Sonzogni, O., Villa, R., Bignazzi, R., and Montesissa, C., 1993, Pharmacokinetic profile of sulphamonomethoxine-trimethoprim in horses after intravenous, intramuscular and oral administration, Res. Vet. Sci.,54:184.PubMedCrossRefGoogle Scholar
  5. Davitiyananda, D., and Rasmussen, E, 1974, Half-lives of sulfadoxine and trimethoprim after single intravenous infusion in cows, Acta Vet. Scand., 15:356.PubMedGoogle Scholar
  6. Droy, B.F., Goodrich, M.S., Lech, J.J., and Kleinow, K.M., 1990, Bioavailability, disposition and pharmacokinetics of ormetoprim in rainbow trout (Salmo gairdneri), Xenobiotica,20:147.PubMedCrossRefGoogle Scholar
  7. Gibson, G.G., and Skett, E, 1986, Introduction to Drug Metabolism Chapman and Hall, New York.Google Scholar
  8. Grondel, J.L., Nouws, J.F.M., and Haenen, O.L.M., 1986, Fish and antibiotics: Pharmacokinetics of sulphadimidine in carp (Cyprinus carpio), Vet. Immunol. Immunopathol., 12:281.PubMedCrossRefGoogle Scholar
  9. Hara, T., Inoue, S., and Saito, M., 1967, Concentration of sulfonamides in the tissue of rainbow trout after oral dosage of the sodium salts, Bull. Jpn. Soc. Sci. Fish., 33:624.CrossRefGoogle Scholar
  10. Hara, T., and Inoue, S., 1967, Maintenance dose of tissue levels of sulfamonomethoxine in rainbow trout after oral administration, Fish Path. 1:35.CrossRefGoogle Scholar
  11. Hara, T., and Inoue, S., 1969, Blood levels of sulfamonomethoxine in rainbow trout after oral administration, Fish Path., 3:9.CrossRefGoogle Scholar
  12. Ishida, N., 1989, Metabolites of five sulfa drugs in the bile and urine of rainbow trout, Nippon Suisan Gakkaishi, 55:2163.CrossRefGoogle Scholar
  13. Kleinow, K.M., Beilfuss, W.L., and Lech, J.J., 1987, Pharmacokinetics of sulfadimethoxine in free swimming trout. Toxicologist, 7:20.Google Scholar
  14. Kleinow, K.M., and Lech, J.J., 1988, A review of the pharmacokinetics and metabolism of sulfadimethoxine in the rainbow trout (Salmo gairdneri), Vet. Human Toxicol, 30:26.Google Scholar
  15. Kleinow, K.M., Beilfuss, W.L., Jorboe, H.H., Droy, B.F., and Lech, J.J., 1992, Pharmacokinetics, bioavailability, distribution, and metabolism of sulfadimethoxine in the rainbow trout (Oncorhynchus mykiss), Can. J. Fish. Aquat. Sci., 49:1070.CrossRefGoogle Scholar
  16. Matsushima, M., Matsubara, S., Ai, K., and Inoue, S., 1971, Toxicity of sulfa drugs in yellowtail, Fish Path.,5:112.CrossRefGoogle Scholar
  17. Michel, C.M.F., Squibb, K.S., and O’Connor, J.M., 1990, Pharmacokinetics of sulphadimethoxine in channel catfish (Ictalurus punctatus), Xenobiotica, 20:1299.PubMedCrossRefGoogle Scholar
  18. Nielsen, P., and Rasmussen, F., 1977, Half-life, apparent volume of distribution and protein-binding for some sulfonamides in cows, Res. Vet. Sci., 22:205.PubMedGoogle Scholar
  19. Nouws, J.F.M., Vree, T.B., Baakman, M., and Tijhuis, M., 1983, Effect of age on the acetylation and deacetylation reactions of sulphadimidine and N4-acetylsulphadimidine in calves, J. Vet. Pharmacol. Ther., 6:13.PubMedCrossRefGoogle Scholar
  20. Rasmussen, F., Gelsa, H., and Nielsen, E, 1979, Pharmacokinetics of sulfadoxine and trimethoprim in horses. J. Vet. Pharmac. Ther., 2:245–255 (1979).CrossRefGoogle Scholar
  21. Shimoda, M., Tsuboi, T., Kokue, E., and Hayama, T., 1983, Dose-dependent pharmacokinetics of intravenous sulfamonomethoxine in pigs, Jpn. J. Pharmacol., 33:3903.CrossRefGoogle Scholar
  22. Shimoda, M., Okamoto, K., Sikazwe, G., Fujii, C., and Son, D.S., 1997, Deacetylation as a determinant of sulphonamide pharmacokinetics in pigs, Vet. Q.,19:186.PubMedCrossRefGoogle Scholar
  23. Souich, P.D., McLean, A.J., Lalka, D., Jenkins, E.L., Haegele, K.D., and McNay, J.L., 1978, Sulfadiazine hand-ling in the rabbit. 1. Pseudosaturation of N-acetyltransferase, J. Pharmacol. Exp. Ther, 7:221.Google Scholar
  24. Squibb, K.S., Michel, C.M.F., Zelikoff, J.T., and O’Connor, J.M., 1988, Sulfadimethoxine pharmacokinetics and metabolism in the channel catfish (Ictalurus punctatus), Vet. Human Toxicol., 30:31.Google Scholar
  25. Tanaka, J., 1977, Expatiation on Fish Drugs, Soft Science Inc., Tokyo.Google Scholar
  26. Ueno, R., Horiguchi, Y., and Kubota, S.S., 1988a, Levels of oxolinic acid in cultured yellowtail after oral administration, Nippon Suisan Gakkaishi, 54:479.CrossRefGoogle Scholar
  27. Ueno, R., Okumura, M., Horiguchi, Y., and Kubota, S.S., 1988b, Levels of oxolinic acid in cultured rainbow trout and amago salmon after oral administration, Nippon Suisan Gakkaishi, 54:485.CrossRefGoogle Scholar
  28. Ueno, R., Uno, K., and Aoki, T., 1994, Pharmacokinetics of sulphamonomethoxine in cultured yellowtail after oral administration, Food Research International. 27:33.CrossRefGoogle Scholar
  29. Ueno, R., Uno, K., and Aoki, T., 1995, Pharmacokinetics and bioavailability of oxytetracycline in cultured yellowtail Seriola quinqueradiata, Dis. in Asian Aquacul., 2:523.Google Scholar
  30. Ueno, R., 1998, Pharmacokinetics and bioavailability of sulphamonomethoxine in cultured eel, Fish Path., 33:000.CrossRefGoogle Scholar
  31. Uno, K., Aoki, T., and Ueno, R., 1992a, Pharmacokinetic study of oxytetracycline in cultured rainbow trout, amago salmon, and yellowtail, Nippon Suisan Gakkaishi, 58:1151.CrossRefGoogle Scholar
  32. Uno, K., Aoki, T., and Ueno, R., 1992b, Pharmacokinetics of nalidixic acid in cultured rainbow trout and amago salmon, Aquaculture,102:297.CrossRefGoogle Scholar
  33. Uno, K., Aoki, T., and Ueno, R., 1993, Pharmacokinetics of sulphamonomethoxine and sulphadimethoxine following oral administration to cultured rainbow trout (Oncorhynchus mykiss). Aquaculture,115:209.CrossRefGoogle Scholar
  34. Uno, K., Aoki, T., and Ueno, R., 1993, Pharmacokinetics of sodium nifurstyrenate in cultured yellowtail after oral administration, Aquaculture,116:331.CrossRefGoogle Scholar
  35. Uno, K., Aoki, T., Ueno, R., and Maeda, I., 1997, Pharmacokinetics and metabolism of sulphamonomethoxine in rainbow trout (Oncorhynchus mykiss) and yellowtail (Seriola quinqueradiata) following bolus intravascular administration, Aquaculture, 153:1.CrossRefGoogle Scholar
  36. van Ginneken, V.J.T., Nouws, J.F.M., Grondel, J.L., Driessens, E, and Degen, M., 1991, Pharmacokinetics of sulphadimidine in carp (Cyprinus carpio L.) and rainbow trout (Salmo gairdneri Richardson) acclimated at two different temperature levels, Vet. Q., 13:88.PubMedCrossRefGoogle Scholar
  37. Vree, T.B., O’Reilly, WJ., Hekster, Y.A., Damsma, J.E., and vander Kleijin, E., 1980, Determination of the acetylator phenotype and pharmacokinetics of some sulfonamides in man, Clin. Pharmacokinet., 5:274.PubMedCrossRefGoogle Scholar
  38. Vree, T.B., Hekster, Y.A., Damsma, J.E., Tijhuis, M., and Friesen, W.T., Pharmacokinetics and mechanism of renal excretion of short acting sulfonamides and N4-acetylsulfonamide derivatives in man, Eur. J. Clin. Pharmacol., 20:283.Google Scholar
  39. Vree, T.B., Reekers-Kitting, J.J., Hekster, C.A., and Nouws, J.F.M., 1983, Acetylation and deacetylation of sulfonamides in dogs, J. Vet. Pharmacol. Ther. 6:153.PubMedCrossRefGoogle Scholar
  40. Vree, T.B., BenekenKolmer, E.W.J., Martea, M., Bosch, R., Hekster, Y.A., and Shimoda, M., 1990a, Pharmacokinetics, N4-glucuronidation and N4-acetylation of sulfadimethoxine in man, Pharm. Weekbl. Sci., 12:51.CrossRefGoogle Scholar
  41. Vree, T.B., BenekenKolmer, E.W.J., Martea, M., Bosch, R., and Shimoda, M., 1990b, High-performance liquid chromatography of sulphadimethoxine and its N4-glucuronide, N4-acetyl and N4-acetyl- N 1glucuronide metabolites in human plasma and urine, J. Chromatogr., 526:119.CrossRefGoogle Scholar
  42. Wagner, J.G., and Nelson, E., 1964, Kinetic analysis of blood levels and urinary excretion in the absorptive phase after single doses of drug, J. Pharm. Sci., 53:1392.PubMedCrossRefGoogle Scholar
  43. Yamaoka, K., Nakagawa, T., and Uno, T., 1978, Application of Akaike’s information criterion (AIC) in the evaluation of linear pharmacokinetic equations, J. Pharmacokinet. Biopharm., 6:165.PubMedGoogle Scholar
  44. Yamaoka, K., Tanigawara, Y., Nakagawa, T., and Uno, T., 1981, A pharmacokinetic analysis program (MULT) for microcomputer, J. Pharmacobio-Dyn., 4:879.PubMedCrossRefGoogle Scholar
  45. Yamaoka, K., and Tanigawara, Y., 1983, Statistical moments, In: Pharmacokinetics Using Personal Computer, Nankoh-doh Press, Tokyo.Google Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Ryuji Ueno
    • 1
  1. 1.Faculty of BioresourcesMie UniversityTsuJapan

Personalised recommendations