Steady state kinetics of 14C-sulfamethazine [4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene[U-14C]sulfonamide] metabolism in swine.
Swine were dosed orally with 14C-sulfamethazine [4-amino-N-(4, 6-dimethyl-2-pyrimidinyl)benzene[U-14C]sulfonamide] for 3, 5, or 7 days (two 165-mg doses/day; 0.46 muCi/mg) and killed 8 hr after the last dose. The concentration of carbon-14 in the tissues increased by an average of 21% from day 3 to day 5 of dosing. However, there was no further increase from day 5 to day 7, indicating that a steady state level of carbon-14 in the tissues was attained by dosing on 5 consecutive days. Liver, kidney, skeletal muscle, blood, and adipose tissue from all animals were analyzed for 14C-labeled sulfamethazine, N4-acetylsulfamethazine, desaminosulfamethazine [N-(4, 6-dimethyl-2-pyrimidinyl)benzenesulfonamide], and the N4-glucose conjugate of sulfamethazine. The identity of these compounds (the hydrolysis product of N4-glucose conjugate) was confirmed by HLPC and gas-liquid chromatography/mass spectral analysis after methylation. The relative distribution of 14C-sulfamethazine and these metabolites varied somewhat among the tissues analyzed but did not vary within a tissue after different periods of dosing.
Mitchell
A D
AD
Paulson
G D
GD
Zaylskie
R G
RG
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D013418:Sulfamethazine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013552:Swine
D013418:Sulfamethazine