Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous administration of a single dose to sheep

Abstract

Objective—To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep. Animals—9 healthy adult female Suffolk-crossbred sheep. Procedures—Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods. Results—Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean ± SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 ± 24.8 μ•h/mL, 2.4 ± 0.5 μg/mL, and 23.1 ± 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed. Conclusions and Clinical Relevance—Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

Pharmacokinetic and pharmacodynamic characterization of ceftiofur crystalline‐free acid following subcutaneous administration in domestic goats

“…injections at 4‐day interval of CCFA at the dosage of 6.6 mg/kg have been recommended to maintain therapeutic blood concentrations for 10 days (Collard et al ., ). Comparing this study to other ceftiofur PK studies, the C max (3.29 μg⁄mL) was lower than that of calves (6.02 μg⁄mL), but was higher than that of sheep (2.4 μg⁄mL) and of earlier reported value of 2.25 μg⁄mL with CCFA dosing in goats (Courtin et al ., ; Washburn et al ., ; Dore et al ., ; Rivera‐Garcia et al ., ). These differences might have been resulted due to difference in origin and breed of goats and site of injection used in two studies.…”

“…Plasma concentrations of CCFA remained above target drug concentration (0.2 lg⁄mL) for 8.5 days in dairy cow, 9.1 days in beef cattle and 6.6-7.5 days in goats when a single subcutaneous (s.c.)injection of 6.6 mg⁄kg body weight was administered (Hibbard et al, 2002;Van Donkersgoed et al, 2008;Dore et al, 2011). In sheep, serum CCFA concentrations >0.1 lg⁄mL were maintained for shorter period of 2.6-4.9 days (Rivera-Garcia et al, 2014). There are fairly good chances that this formulation is used off-label and/or receives approval for its use in goat species.…”

“…Ceftiofur is the only injectable antimicrobial approved as a daily dosage of 1.1–2.2 mg/kg body weight, by Food and Drug Administration (FDA) in goats for the treatment of respiratory diseases associated with P. multocida and M. haemolytica . Pharmacokinetic properties of ceftiofur have been investigated in cattle (Soback et al ., ; Erskine et al ., ; Brown et al ., , ; Okker et al ., ; von Krueger et al ., ; Gorden et al ., ), camel (Goudah, ), goat (Courtin et al ., ; Dore et al ., ), horse (Collard et al ., ; Credille et al ., ; Fultz et al ., ; Macpherson et al ., ), sheep (Craigmill et al ., ; Rivera‐Garcia et al ., ), pig (Brown et al ., ; Tantituvanont et al ., ; Day et al ., ) and alpacas (Dechant et al ., ). Recently, a long‐acting formulation of ceftiofur, ceftiofur crystalline‐free acid (CCFA) (CCFA‐SS; EXCEDE http://pfizerah.com), has been approved in the United States for the treatment of bovine respiratory disease and foot rot when administered as a single dose of 6.6 mg/kg of body weight.…”

Extralabel drug use in small ruminants

“…When ceftiofur crystalline-free acid is administered SC at a location other than the base of an ear, it can diffuse into the underlying muscle, thereby increasing the risk for violative tissue drug residues. The pharmacokinetics of ceftiofur crystalline-free acid in sheep and goats have been described in multiple studies, [53][54][55] but those studies did not include any data re-garding depletion of tissue drug residues. Consequently, veterinarians should submit a request to FARAD for a recommended WDI whenever ceftiofur crystalline-free acid is administered to sheep and goats.…”

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

“…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).…”