Pharmacokinetic profile of Ceftiofur Hydrochloride Injection in lactating Holstein dairy cows

Abstract

Ceftiofur (CEF), a broad-spectrum third-generation cephalosporin, exhibits a good activity against a broad range of gram-negative and gram-positive bacteria, including many that produce β-lactamase. To design a rational dosage regimen for the drug in lactating Holstein dairy cows, the pharmacokinetic properties of ceftiofur hydrochloride injection were investigated in six cows after intravenous, intramuscular, and subcutaneous administration of single dose of 2.2 mg/kg BW (body weight). Plasma concentration-time curves and relevant parameters were best described by noncompartmental analysis through WinNonlin 6.3 software. After subcutaneous administration, the absolute bioavailability was 61.12% and the T (elimination half-life) was 8.67 ± 0.72 hr. The C (maximum plasma concentration) was 0.88 ± 0.21 μg/ml and T (the time after initial injection to when C occurs) was 1.50 ± 0.55 hr. The MRT (mean residence time) was 11.00 ± 0.30 hr. Following intramuscular administration, the C (1.09 ± 0.21 μg/ml) was achieved at T (1.20 ± 0.26 hr) with an absolute availability of 70.52%. In this study, the detailed pharmacokinetic profiles of free and total CEF showed that this drug is widely distributed and rapidly eliminated and may contribute to a better understanding of the usage of ceftiofur hydrochloride injection in Holstein dairy cows.

Pharmacokinetic Studies Of Ceftiofur (Ceftiprima In Calves)

“…The elimination half life of ceftiofur t0.5(el) subsequent single intramuscular administration was (8.30±0.158 h).This obtained result is similar to those stated in cattle (8.13 and 9.20h, Gorden, et al,2015 andWang et al, 2018) and nearly similar to those results in cattle (10.3h,Hornish and Kotarski 2002),but not similar to the results of intramuscular administration of ceftiofur in calves (3.56,Halsteadet al,1992),buffalo calves (17 h, Sudamrao, 2015),neonatal calves ( 19.9h ,Altanet al,2017),dairy goats (2.6h,Courtinet al, 1997),camels (3.2h,Goudah, 2007, water buffalo (12.72h,Nieet al,2015) and cattle (5.03 and15.3h, Liu et al,2010 andTohamy, 2008).The differences between the value systems calculated for pharmacokinetic parameters can be directly linked to the species of animal, formulations of the drug used, the sex, size or age of the animals, discrepancies in deposits of fatty tissue between breeds or species of animals , and even inter-individual variations, as well as the drug analysis method (Riond et al, 1989).…”

“…This result is not consisted with the results in calves (66.17 ,77.3 and 153μg/ml.h,Halstead et al,1992;Brown et al, 1996 andAltan et al,2017) respectively, buffalo calves (26.8 μg/ml.h, Sudamrao,2015),sheep(33.7μg/ml.h,Cra igmill et al,1997,water buffalo (65.4μg/ml.h, Nie et al,2015) and cattle (163μg/ml.h, Liu et al,2010).This may be because of differences in the quantity of body fluids between species and different ages. The bioavailability of ceftiofur sodium found in this research about 65% that may similar to the result obtained from dairy cows (Wang et al, 2018) that was 70.5%and buffalo calves (Sudamrao, 2015) that was 75%. After 2.2 mg ceftiofur / kg.b.wt single intravenous injection in calves, The drug demonstrates high serum concentration (16.72±0.2μg / ml) in calves at 5 minutes after injection, Then it gradually reduced its concentration until its minimum level reached 24 hours after injection (1.59±0.11μg / ml).…”

“…After comparison to other cephalosporin, the time studied to reach the maximum serum concentration (Tmax) was agreed with those reported in cefqinome in broiler chicken (2.8h,El-Mahdy et al, 2015) The mean peak ceftiofur serum concentration (Cmax) was (6.50±0.12 μg/ml) after intramuscular administration of 2.2 mg ceftiofur /kg.bw these values are consistence with those in water buffalo (6.2μg/ml, Nie et al,2015),buffalo calves (6.6μg/ml ,Sudamrao, 2015), calves (7.73 μg/ml, Altan et al,2017), sheep (7.13μg/ml, Craigmill et al,1997) and cows (7.8μg/ml, Tohamy, 2008). This result not resemble the result had been stated in beef calves (8.78μg/ml Halstead et al,1992, cattle (13.9 ,14.5 ,9.58 and 1.09μg/ml, Brown et al,1996;Hornish and Kotarski 2002;Gorden, et al,2015 andWang et al, 2018) respectively. Even though there are many differences throughout the values of maximum ceftiofur serum levels, the literature on β-lactam antibiotics mentions that effectiveness does not correlate with the maximum concentration of plasma or tissue but depends on the length of time at which the drug levels stay above MIC of the susceptible pathogen (Sudamrao, 2015).…”

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

“…In the current study, the bioavailability was calculated as 82.95% following subcutaneous injection, indicating that ceftiofur was well absorbed in cats. The bioavailability calculated here was greater than that reported in lactating cows (61.12%; Wang et al, ), but similar with that in goats (85.16%; Fernandez–Varon et al, ). Higher bioavailability values (even at 100% in sheep; Craigmill et al, ) were reported for ceftiofur after intramuscular 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).…”