title: Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis.
abstract: The objective of this study was to determine the pharmacokinetics of CCFA in mares with placentitis and evaluate the disposition of the drug in fetal fluids, fetal membranes, colostrum, and serum of foals. A secondary objective was to obtain pilot data regarding the efficacy of CCFA for improving foal survival in mares with placentitis. Twelve pregnant pony mares were enrolled in the study, inoculated with Streptococcus zooepidemicus, intracervically and assigned to one of three groups: CEFT (n = 3; administered CCFA only; 6.6 mg/kg, i.m., q96h); COMBO (n = 6; administered combination therapy of CCFA, altrenogest, and pentoxifylline); UNTREAT (n = 3, no treatment). Treatment was initiated at the onset of clinical signs. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur metabolites, were measured using high-performance liquid chromatography. Maximum and minimum serum concentrations of DCA at steady state in treated mares were 2.40±0.40 μg/mL and 1.06±0.29 μg/mL, respectively. Concentration of DCA in colostrum was 1.51±0.60 μg/mL. DCA concentrations in placenta and fetal tissues were very low (median = 0.03 μg/mL) and below the minimum inhibitory concentration of relevant pathogens. DCA was not detected in amniotic fluid or foal serum. Treatment did not appear to improve foal survival (CEFT: 0/3; COMBO: 2/6; UNTREAT: 2/3). Bacteria were recovered from the uterus of most mares postpartum and from blood cultures of most foals regardless of treatment.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA. macphersonm@ufl.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Macpherson
authors.forename: S
authors.initials: S
authors.lastname: Giguère
authors.forename: J N
authors.initials: JN
authors.lastname: Hatzel
authors.forename: M
authors.initials: M
authors.lastname: Pozor
authors.forename: S
authors.initials: S
authors.lastname: Benson
authors.forename: M
authors.initials: M
authors.lastname: Diaw
authors.forename: L C
authors.initials: LC
authors.lastname: Sanchez
authors.forename: T W
authors.initials: TW
authors.lastname: Vickroy
authors.forename: L
authors.initials: L
authors.lastname: Tell
authors.forename: S
authors.initials: S
authors.lastname: Wetzlich
authors.forename: J
authors.initials: J
authors.lastname: Sims
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002511:Cephalosporins / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003126:Colostrum / Q000737:chemistry; D005321:Extraembryonic Membranes / Q000737:chemistry; D005260:Female; D005333:Fetus / Q000737:chemistry; D006736:Horses / Q000378:metabolism; D010920:Placenta / Q000737:chemistry; D010922:Placenta Diseases / Q000188:drug therapy / Q000662:veterinary*; D011247:Pregnancy
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C063324:desfuroylceftiofur; C053503:ceftiofur