title: Renal tubular excretion of the N4-acetyl metabolites of sulphasomidine and sulphadimethoxine in the dog.
abstract: To investigate whether dogs are able to excrete acetylated drugs by active transport, the plasma kinetics and renal excretion of the N4-acetyl metabolites of sulphasomidine and sulphadimethoxine were studied in the beagle dog after a rapid intravenous bolus injection. Two doses of N4-acetylsulphasomidine (1050 and 105 mg) and one dose of N4-acetylsulphadimethoxine (472 mg) were administered on separate occasions. The renal clearance (CLR) was as follows: N4-acetylsulphasomidine (1050 mg) 34 mL min-1; N4-acetylsulphasomidine (105 mg) 28 mL min-1; and N4-acetylsulphadimethoxine (472 mg) 24 mL min-1. CLR was higher than expected on the basis of the measured glomerular filtration rate, indicating that the N4-acetyl metabolites may be excreted by the renal tubules by active tubular transport. Saturation of the excretion process of N4-acetylsulphasomidine occurred with a transport maximum of 930 +/- 190 micrograms min-1 and a Michaelis-Menten constant of 37 +/- 10 micrograms mL-1. It may be concluded that the dog renal organic anion transport system is able to secrete acetylated sulphonamides.
authors.affiliation: Department of Pharmacology, University of Nijmegen, The Netherlands.
authors.forename: S P
authors.initials: SP
authors.lastname: Boom
authors.forename: A C
authors.initials: AC
authors.lastname: Wouterse
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: C A
authors.initials: CA
authors.lastname: Van Ginneken
authors.forename: F G
authors.initials: FG
authors.lastname: Russel
mesh_terms: D000107:Acetylation; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005919:Glomerular Filtration Rate; D007275:Injections, Intravenous; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D012044:Regression Analysis; D013412:Sulfadimethoxine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D013443:Sulfisomidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
chemical_list: C038180:N(4)-acetylsulfadimethoxine; D013412:Sulfadimethoxine; C083475:N(4)-acetylsulphasomidine; D013443:Sulfisomidine