title: Dose dependent disposition of sulphadimidine and of its N4-acetyl and hydroxy metabolites in plasma and milk of dairy cows.
abstract: The disposition of sulphadimidine (SDM) and of its N4-acetyl (N4-SDM) and two hydroxy metabolites, 6-hydroxymethyl-(SCH2OH) and 5-hydroxyasulphadimidine (SOH), was studied in plasma and milk of dairy cows following intramuscular or intravenous administration of sulphadimididine-33.3% at doses of 10, 45, 50, and 100 mg/kg. The main metabolite in plasma as well as in milk was SCH2OH. The metabolite percentages, the final plasma elimination half-lives, and the time of peak SDM concentrations in milk are presented for different dosages. The concentrations of SDM and its metabolites in milk ran parallel to those in plasma beyond 4 hours p.i. The metabolite concentrations in plasma and milk were lower than those of the parent SDM. Sulphate and glucuronide metabolites could not be detected in milk. At high doses (45 mg/kg or more) and SDM plasma concentrations exceeding 20 micrograms/ml, a capacity limited metabolism of SDM to SCH2OH was noticed, viz. a steady state concentration of SCH2OH and a biphasic elimination pattern for SDM and SCH2OH in plasma and milk. The mean ultrafiltrate ratios of the milk to plasma concentrations with respect to SDM, SCH2OH, SOH, and N4-SDM were: 0.69, 0.22, 020, and 0.63, respectively. The total amount of SDM and its metabolites recovered from the milk after milking twice daily over the whole experimental time was less than 2% of the applied dose. A bioassay method allowed of detecting qualitatively SDM concentrations exceeding 0.2 micrograms/ml in plasma or milk. Withholding times for edible tissues and milk are suggested.
mesh_terms: D000818:Animals; D002417:Cattle / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008892:Milk / Q000378:metabolism*; D011485:Protein Binding; D013418:Sulfamethazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*
chemical_list: C032633:N-acetylsulfamethazine; D013418:Sulfamethazine; C046744:5-hydroxysulfadimidine; C046745:6-hydroxymethylsulfadimidine