Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares.
Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg/kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (beta-haemolytic streptococci) ranged from 0.25-2 and 1.5-3.0 microg/mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg/kg respectively. After i.v. treatment with EFX at 5 mg/kg, endometrial concentrations of EFX and CFX above the MIC value were detected for 36-48 and 22-43 h posttreatment for Gram-negative and -positive isolates respectively. Concentrations above MIC were maintained for much shorter periods at the lower (2.5 mg/kg) treatment dose. Based on these results, a conventional dose (5 mg/kg) of EFX given prebreeding followed by two further doses at 36-48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis.
González
C
C
Laboratory of Pharmacology, Faculty of Veterinary Medicine, Universidad Nacional del Centro de la Provincia de Buenos Aires, Buenos Aires, Argentine.
Moreno
L
L
Fumuso
E
E
García
J
J
Rivulgo
M
M
Confalonieri
A
A
Sparo
M
M
Sánchez Bruni
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D056148:Chromatography, Reverse-Phase / Q000662:veterinary; D002939:Ciprofloxacin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D004716:Endometritis / Q000517:prevention & control / Q000662:veterinary*; D004717:Endometrium / Q000737:chemistry; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006734:Horse Diseases / Q000517:prevention & control*; D006736:Horses; D007275:Injections, Intravenous / Q000662:veterinary; D008826:Microbial Sensitivity Tests / Q000662:veterinary
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin