Pharmacokinetics of ceftiofur sodium in pregnant pony mares

Abstract

Placentitis is a common cause of pregnancy loss in the mare. Effective treatments for placentitis remain elusive. Ceftiofur sodium is effective against the most common pathogens causing placentitis, including Streptococcus equi subspecies zooepidemicus. However, little is known about the pharmacokinetics of the drug in pregnant mares or whether or not the drug penetrates the fetal placental barrier. Eight pregnant pony mares were treated with ceftiofur sodium (Naxcel®)(4.4mg/kg, IM, q24h) for at least 4 days prior to induction of parturition. Mares were monitored daily for signs of onset of parturition and mammary secretions were tested daily for calcium concentrations using a commercial test. Parturition was induced using oxytocin (5 IU) administered at 25 minute intervals until the onset of parturition. Allantoic fluid, amniotic fluid and pre-suckle colostrum samples were collected. Plasma samples were collected at 2 hours post drug administration in the mare, and at birth (time point 0) and at 1,2,4,8, and 24 hours after delivery from mares and foals. Plasma samples were analyzed using high performance liquid chromatography to detect concentrations of ceftiofur and its active metabolite, desfuroylceftiofur acetamide (DCA). Median plasma concentrations of DCA of 8.61 (7.38-8.89) μg/ml were found at birth in the mare, while no detectable concentrations of the drug were found in foal plasma. Median DCA concentrations of 1.70 (1.30-1.75) μg/ml were found in milk. No detectable amounts of the drug were found in either the allantoic or amniotic fluid. Results from this study show that therapeutic concentrations of ceftiofur sodium seem not to attain the fetal compartment or foal plasma after drug administration to the mare prior to delivery. These data suggest that ceftiofur sodium does not penetrate the equine feto-placental barrier and, therefore, may not be effective for treating mares with placentitis.