Disposition of sulfadimidine and its N4-acetyl and hydroxy metabolites in horse plasma.
The plasma disposition of sulfadimidine (SDM) and its metabolites N4-acetylsulfadimidine (N4-SDM), 6-hydroxymethyl-4-methyl-pyrimidine (SCH2OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross-over trials. The percentages of N4-SDM (0.58-0.90%), SOH (0.83-6.75%) and SCH2OH (0.38-0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/kg), the elimination half-life was slightly longer than at low doses (6.0, 10.5, 11.0 vs 5.0, 9.5, 9.5, respectively). The plasma protein binding was related to the dose; it was for the 20 and 200 mg/kg doses, respectively:SDM:61.5-73.3% and 50.5-52.1%; SOH: 47.1-71.0% and 36.7-39.5%, and for N4-SDM: 45.9-63.2% and 38.3-53.7%. The protein binding for SCH2OH, measured in samples obtained at the high dose level, ranged from 13.8 to 20.0%.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D006736:Horses / Q000097:blood*; D007275:Injections, Intravenous; D007700:Kinetics; D010949:Plasma / Q000378:metabolism; D011485:Protein Binding; D013418:Sulfamethazine / Q000031:analogs & derivatives / Q000097:blood*; D014462:Ultrafiltration
D001798:Blood Proteins; C032633:N-acetylsulfamethazine; D013418:Sulfamethazine; C046744:5-hydroxysulfadimidine; C046745:6-hydroxymethylsulfadimidine