title: Effect of tick-borne fever (Ehrlichia phagocytophila) and trypanosomiasis (Trypanosoma brucei 1066) on the pharmacokinetics of sulfadimidine and its metabolites in goats.
abstract: The effect of tick-borne fever (TBF) and trypanosomiasis (TBR) on the plasma disposition of sulfadimidine (SDD) in goats was studied after iv administration of 20 and 200 mg/kg of body weight. In each group of six goats, the plasma disappearance curves showed four animals with rapid and two with slow SDD elimination. It is likely that this difference is determined by oxidative rather than acetylation phenotype. In all goats administered 20 mg/kg, half-life increased with TBF but not with TBR. Vd(beta) decreased with both infections. With 200 mg/kg, Vd did not change, whereas AUC and MRT increased with both infections. Metabolites were examined in TBF experiments: N4-acetyl-SDD (N4Ac), 6-hydroxymethyl-SDD (CH2OH) and its glucuronide, 5-hydroxy-SDD (SOH) and its glucuronide, and 6-carboxy-SDD (COOH) and its glucuronide (COOH-glu). At low dose (20 mg/kg), TBF caused the proportion of dose recovered from urine as unchanged SDD to be halved, whereas N4Ac increased correspondingly (2x). After the high dose (200 mg/kg), elimination was saturated and changes in proportional recovery of SDD in urine were less. However, the N4Ac proportion was still doubled, in contrast to the other metabolites, suggesting that saturation was caused by oxidations rather than by acetylation. Formation of CH2OH was the same in health and disease after the low dose, but glucuronidation dropped from 20% to 4% (rapid) or 7% (slow) of total CH2OH.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Gogh
authors.forename: A D
authors.initials: AD
authors.lastname: Watson
authors.forename: J F
authors.initials: JF
authors.lastname: Nouws
authors.forename: J
authors.initials: J
authors.lastname: Nieuwenhuijs
authors.forename: A S
authors.initials: AS
authors.lastname: van Miert
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004536:Ehrlichia; D005260:Female; D006041:Goats / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008297:Male; D008657:Metabolic Clearance Rate; D012288:Rickettsiaceae Infections / Q000378:metabolism / Q000662:veterinary*; D013418:Sulfamethazine / Q000493:pharmacokinetics*; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000378:metabolism / Q000662:veterinary*
chemical_list: D013418:Sulfamethazine