Evaluation of an extended‐release formulation of ceftiofur crystalline‐free acid in koi (Cyprinus carpio)

Abstract

The use of an extended release ceftiofur crystalline-free acid formulation (CCFA, Excede For Swine(®) , Pfizer Animal Health) in koi was evaluated after administration of single intramuscular (i.m.) or intracoelomic (i.c.) doses. Twenty koi were divided randomly into a control group and four treatment groups (20 mg/kg i.m., 60 mg/kg i.m., 30 mg/kg i.c., and 60 mg/kg i.c.). Serum ceftiofur-free acid equivalents (CFAE) concentrations were quantified. The pharmacokinetic data were analyzed using a nonlinear mixed-effects approach. Following a CCFA injection of 60 mg/kg i.m., time durations that serum CFAE concentrations were above the target concentration of 4 μg/mL ranged from 0.4 to 2.5 weeks in 3 of 4 fish, while serum CFAE concentrations remained below 4 μg/mL for lower doses evaluated. Substantial inter-individual variations and intra-individual fluctuations of CFAE concentrations were observed for all treatment groups. Histological findings following euthanasia included aseptic granulomatous reactions, but no systemic adverse effects were detected. Given the unpredictable time vs. CFAE concentration profiles for treated koi, the authors would not recommend this product for therapeutic use in koi at this time. Further research would be necessary to correlate serum and tissue concentrations and to better establish MIC data for Aeromonas spp. isolated from naturally infected koi.

Pharmacokinetics of Single Intramuscular Administration of Ceftiofur Crystalline Free Acid in American Alligators (Alligator Mississippiensis)

“…Flip-flop kinetics for CFFA has been observed in multiple species as compared to immediate-release formulations, including lowerorder species such as green iguana and koi (Cyprinus carpio). 12,23,31 In examining the disposition of ceftiofur equivalents over time, each animal in this study was found to have a variable small secondary peak in drug concentrations at one time point between 120 and 366 h postdose following a decline in drug concentrations. This may represent variable absorption rates of long-acting ceftiofur formulations.…”

“…5,13 Drug administration and sample collection A 30-mg/kg dose of CCFA (Excede w 200 mg/ml, Zoetis) was administered intramuscularly in the left triceps muscle of each individual. Up to 1 ml of whole blood was collected from the lateral occipital sinus before injection (Time 0), and at 4,12,24,48,72,120,144,192,288, and 366 h postinjection. Blood was placed directly into lithium heparin tubes and kept at room temperature for transport to the laboratory for plasma separation.…”

“…A single intramuscular dose of 30 mg/kg was administered in the triceps muscle. Blood samples were collected prior to treatment and at 4, 12,24, 48, 72, 120, 144, 192, 288, and 366 h post administration. Plasma samples were analyzed for ceftiofur equivalent concentrations using liquid chromatography-mass spectrometry.…”

Estimation of pharmacological properties of ceftiofur, an injectable cephalosporin antibiotic, for treatment of streptococcosis in cultured olive flounderParalichthys olivaceus

“…It was similarly short in tilapia when CS was examined in the fish (Khalil et al., 2016). In contrast to the highly water‐soluble chemical form of CS used in this study, the t 1/2 was extremely long (583.8 hr) when a water‐insoluble formula (ceftiofur free base) was injected to koi carp (Grosset et al., 2015). It would be reasonable to ascribe the striking difference to body residence time of the drug between koi (Khalil et al., 2016) and olive flounder or tilapia to the chemical formula, rather than to fish species.…”

“…Pharmacokinetic profiles of CS or its base form (ceftiofur) have been assessed in various livestock animals such as dairy cows, horses, sheep, camels and deer (Craigmill et al., 1997; Drew et al., 2004; Foster et al., 2016; Fultz et al., 2015; Garrett et al., 2015; Goudah, 2007; Rivera‐Garcia et al., 2014; Wang, 2015). In contrast, pharmacokinetic information in fish species is rare reports being available only from tilapia and carp (Grosset et al., 2015; Khalil et al., 2016; Somjetlertcharoen, 2001).…”