title: Plasma disposition and renal clearance of sulphadimidine and its metabolites in laying hens.
abstract: Plasma disposition of sulphadimidine (SDM) and its metabolites was studied in laying hens after 100 mg SDM kg-1 doses were administered as a single intravenous dose, a single oral dose and multiple oral doses once daily for five consecutive days. SDM was extensively metabolised by acetylation and hydroxylation. In plasma, the metabolite observed with the highest concentration was N4-acetylsulphadimidine (N4-SDM) followed by hydroxymethylsulphadimidine (CH2OH) and 5-hydroxysulphadimidine. Following intravenous administration a biphasic elimination (as seen for a capacity limited reaction) pattern for SDM and its metabolites was observed. Multiple (5x) SDM dosing revealed plasma SDM concentrations ranging between 7 and 108 micrograms ml-1; within 96 hours of termination of the multiple SDM dosing, the plasma SDM concentration was below 0.01 micrograms ml-1. The renal clearances of N4-SDM and the hydroxy metabolites were approximately 10 times greater than that of SDM. The SDM mass balance (faecal/urinary recovery) showed a loss of 56 per cent after intravenous dosage and of 67 per cent after a single oral dosage; the hydroxy metabolites accounted for the highest percentage in faeces/urine. Thus additional metabolic pathways must exist in laying hens.
authors.affiliation: Department of Experimental Animal Morphology and Cell Biology, Agricultural University, Wageningen, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Nouws
authors.forename: M F
authors.initials: MF
authors.lastname: Geertsma
authors.forename: J L
authors.initials: JL
authors.lastname: Grondel
authors.forename: M M
authors.initials: MM
authors.lastname: Aerts
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: C A
authors.initials: CA
authors.lastname: Kan
mesh_terms: D000107:Acetylation; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens / Q000378:metabolism*; D005260:Female; D006900:Hydroxylation; D007275:Injections, Intravenous / Q000662:veterinary; D007668:Kidney / Q000378:metabolism; D011485:Protein Binding; D013418:Sulfamethazine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D013418:Sulfamethazine