RENAL TUBULAR EXCRETION OF THE N4-ACETYL METABOLITES OF SULPHASOMIDINE AND SULFADIMETHOXINE IN THE DOG

To investigate whether dogs are able to excrete acetylated drugs by ac tive transport, the plasma kinetics and renal excretion of the N4-acet yl metabolites of sulphasomidine and sulphadimethoxine were studied in the beagle dog after a rapid intravenous bolus injection. Two doses o f N4-acetylsulphasomidine (1050 and 105 mg) and one dose of N4-acetyls ulphadimethoxine (472 mg) were administered on separate occasions. The renal clearance (CL(R)) 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. CL(R) was higher than e xpected on the basis of the measured glomerular filtration rate, indic ating that the N4-acetyl metabolites may be excreted by the renal tubu les by active tubular transport. Saturation of the excretion process o f N4-acetylsulphasomidine occurred with a transport maximum of 930 +/- 190 mug min-1 and a Michaelis-Menten constant of 37 +/- 10 mug mL-1. It may be concluded that the dog renal organic anion transport system is able to secrete acetylated sulphonamides.