Pharmacokinetics of ceftiofur sodium in equine pregnancy

Abstract

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 μg/ml (low dose) and 7.45 ± 1.05 μg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 μg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 μg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 μg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Pharmacokinetics of ceftiofur sodium in cats following a single intravenous and subcutaneous injection

“…Similar half-lives (p = .406) were calculated in cats following a single intravenous and subcutaneous injection (11.29 and 10.69 hr, respectively). Longer half-live (18.1 hr) was reported for ceftiofur sodium in neonatal calves (Woodrow et al, 2016); however, shorter ones were reported in pregnant pony mares (ranging from 2.91 to 4.1 hr; Macpherson et al, 2017) and sheep (in the range of 4.87-7.75 hr; Craigmill et al, 1997). These inconsistencies may be due to the differences in eating habits and/or physiological status.…”

“…The pharmacokinetics profiles of ceftiofur have been determined in horses (Collard et al, 2011;Edwards, Khalfan, Jacobson, Pirie, & Raidal, 2017;Macpherson et al, 2017;Meyer et al, 2009), cattle (Foster, Jacob, Warren, & Papich, 2016;Gorden et al, 2018;Jaglan et al, 1990;Kang et al, 2018;Okker et al, 2002;Wang et al, 2018;Woodrow, Caldwell, Cox, Hines, & Credille, 2016), water buffalo (Nie et al, 2016), camels (Goudah, 2007), goats (Courtin, Craigmill, Wetzlich, Gustafson, & Arndt, 1997;Fernandez-Varon, Carceles-Garcia, Serrano-Rodriguez, & Carceles-Rodriguez, 2016;Waraich, Sidhu, Daundkar, Kaur, & Sharma, 2017), sheep (Craigmill, Brown, Wetzlich, Gustafson, & Arndt, 1997;Nagel, Beltran, Molina, & Althaus, 2012;Rivera-Garcia et al, 2014), elephants (Dumonceaux, Isaza, Koch, & Hunter, 2005), pigs (Sparks et al, 2017;Xiong et al, 2018), avian species (Tell et al, 1998), and fish (Khalil, Shaheen, & Abdou, 2016). Among different species, ceftiofur shared some similar pharmacokinetics behaviors, such as relatively poor distribution, but quick and complete transformation to its active metabolites, desfuroylceftiofur (DCE), and desfuroylceftiofur conjugates (DCEC).…”

Ceftiofur use and antimicrobial stewardship in the horse

“…Practitioners should consult culture and sensitivity results and consider use of first line antimicrobials, or local therapies, before considering treatment with ceftiofur. In contrast to support for treatment of endometrial infection, ceftiofur is not useful for treating placentitis in mares 83,84 …”

“…In contrast to support for treatment of endometrial infection, ceftiofur is not useful for treating placentitis in mares. 83,84 5.6 | Use of ceftiofur for Lyme disease A full discussion of the complex disease processes that occur with Lyme disease is beyond the scope of this review. However, as ceftiofur has been recommended by some practitioners for the treatment of Lyme, we have included results of one study utilising ceftiofur treatment.…”