Renal tubular excretion of the N4-acetyl metabolites of sulphasomidine and sulphadimethoxine in the dog.
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.
Boom
S P
SP
Department of Pharmacology, University of Nijmegen, The Netherlands.
Wouterse
A C
AC
Vree
T B
TB
Van Ginneken
C A
CA
Russel
F G
FG
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
C038180:N(4)-acetylsulfadimethoxine; D013412:Sulfadimethoxine; C083475:N(4)-acetylsulphasomidine; D013443:Sulfisomidine