Spa. Boom et al., RENAL TUBULAR EXCRETION OF THE N4-ACETYL METABOLITES OF SULPHASOMIDINE AND SULFADIMETHOXINE IN THE DOG, Journal of Pharmacy and Pharmacology, 45(7), 1993, pp. 614-617
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.