| Reference | [1]. Clin Toxicol (Phila). 2008 Nov;46(9):908-10. doi: 10.1080/15563650801955278.<br />
Accidental human injection of Excenel RTU: ceftiofur hydrochloride in cottonseed oil.<br />
Gwynne-Jones D(1), Lyall P, Hung NA, Meikle G.<br />
Author information: (1)Dunedin Hospital, Orthopaedics, and Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. [email protected]<br />
INTRODUCTION: There is little knowledge within the medical community of the existence of veterinary antibiotics in oil-based suspensions and the adverse effects that may occur with accidental human injection. CASE REPORT: A farmer injected an unknown quantity of Excenel RTU into her right thigh. Despite early debridement she developed a deep infection and recurrent chronic inflammation in the subcutaneous tissues and muscle secondary to the cottonseed oil suspension. Radical debridement and extensive split skin grafting was required but she still has had recurrences 12 months after injury. DISCUSSION: Prompt surgical debridement should be performed as in cases of oil based veterinary vaccines. Despite being an antibiotic there is a significant risk of infection from a dirty needle following inoculation and multiple cultures should be taken and appropriate broad spectrum antibiotics used. Radical debridement and skin grafting necessitating specialist plastic surgical attention may be required.<br />
DOI: 10.1080/15563650801955278 PMID: 18608258 [Indexed for MEDLINE]<br />
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[2]. Curr Drug Deliv. 2021;18(2):224-233. doi: 10.2174/1567201817666200903165119.<br />
Formulation, Characterization and Pharmacokinetics of Long-acting Ceftiofur Hydrochloride Suspension.<br />
Xie S(1), Zhang X(1), Luo W(1), Meng K(1), Chen D(2), Pan Y(1), Tao Y(2), Huang L(2), Liu Z(2), Wang Y(2), Yuan Z(1).<br />
Author information: (1)National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University (HZAU), Wuhan, Hubei 430070, China. (2)MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.<br />
OBJECTIVE: A ceftiofur hydrochloride long-acting oily suspension with no irritation was prepared by testing and optimizing the types and amounts of organic solvents, suspending agents, and surfactants. METHODS: Its properties, stability, injection site irritation, in vitro release, and pharmacokinetics in pigs were evaluated. The optimum formulation was used ethyl oleate, aluminum monosterate, and span-80 as organic solvents, suspending agents, and surfactant, respectively. The drug microparticles were uniform long strip with size of 1.53 ± 0.11 μm and no agglomerations, and were evenly dispersed. The re-dispersed time, sedimentation rate and pH value of the suspension were 4 s under a magnetic shaker rotating at 20 r/min, 1 and 5.0, respectively. It could go through 7-gage needle smoothly with withdrawal volume of 9.9 mL/min. RESULTS: The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration, the drug concentration above 0.15 μg/mL was last for 120 h. Its elimination half-life (T1/2ke), mean residence time (MRT), and bioavailability were increased by 1.73, 1.62, and 2.16 times compared to Excenel®. CONCLUSION: The results suggested that the suspension had excellent sustained-release and will make ceftiofur hydrochloride more effective and convenient to use.<br />
DOI: 10.2174/1567201817666200903165119 PMID: 32885750<br />
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[3]. J Vet Med Sci. 2018 Dec 11;80(12):1847-1852. doi: 10.1292/jvms.18-0470. Epub 2018 Nov 1.<br />
Bioequivalence evaluation of two 5% ceftiofur hydrochloride sterile suspension in pigs.<br />
Xiong J(1)(2), Zhu Q(1)(2), Lei Z(1)(2), Yang S(1)(2), Chen P(1), Zhao Y(1)(2), Cao J(1)(2), Qiu Y(3).<br />
Author information: (1)Department of Veterinary Pharmacology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. (2)National Reference Laboratory of Veterinary Drug Residues and Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan 430070, China. (3)School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, China.<br />
The purpose of this study was to evaluate the bioequivalence of 5% ceftiofur hydrochloride sterile suspension in two formulations, a test formulation (Saifukang 5% CEF, Hvsen) and a reference formulation (Excenel®RTU 5% CEF, Pfizer). Twenty-four healthy pigs were assigned to a two-period, two-treatment crossover parallel trial, and both formulations were administered at a single intramuscular dose of 5 mg/kg weight, with a 7-day washout period. Blood samples were collected consecutively for up to 144 hr after administration. The concentrations of ceftiofur- and desfuroylceftiofur-related metabolites in the plasma were determined by high-performance liquid chromatography. In addition, the major pharmacokinetic parameters (Cmax, AUC0-t and AUC0-∞) were computed and compared via analysis of variance, with 90% confidence intervals. Bioequivalence evaluation of Tmax was statistically analyzed with the nonparametric test. The comparison values between test and reference formulation for AUC0-t, AUC0-∞, Cmax, and Tmax were 376.7 ± 75.3 µg·hr/ml, 390.5 ± 78.6 µg·hr/ml, 385.9 ± 79.2 µg·hr/ml, 402.7 ± 80.4 µg·hr/ml, 34.6 ± 5.5 µg/ml, 36.1 ± 6.2 µg/ml, 1.27 ± 0.18 hr, and 1.26 ± 0.21 hr, respectively, and we observed no significant differences between the two formulations. The 90% CI values were within the recommended range of 80-125% (P>0.05), and the relative bioavailability of the test product was 96.47 ± 10.92% according to AUC0-t values. Based on our results, the two formulations exhibit comparable pharmacokinetic profiles, and the test product is bioequivalent to the reference formulation.<br />
DOI: 10.1292/jvms.18-0470 PMCID: PMC6305520 PMID: 30381675 [Indexed for MEDLINE]<br />
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[4]. J Equine Vet Sci. 2020 Dec;95:103295. doi: 10.1016/j.jevs.2020.103295. Epub 2020 Oct 12.<br />
Ceftiofur Side Effect in a Mare-Case Report.<br />
Pradella GD(1), Taschetto PM(2), Duarte CA(3), da Silva Azevedo M(3), Góss GC(2).<br />
Author information: (1)Universidade Federal do Pampa (UNIPAMPA), Uruguaiana, RS. Electronic address: [email protected]. (2)Master's Student at Universidade Federal do Pampa (UNIPAMPA), Uruguaiana, RS. (3)Researcher Teacher at Universidade Federal do Pampa (UNIPAMPA), Uruguaiana, RS.<br />
Adverse drug reactions in horses are rare. The antimicrobials are in the list of the most common drugs associated with reaction in horses. The aim of this report is to describe the clinical presentation of an adverse drug reaction after the intramuscular administration of ceftiofur hydrochloride. A 5-year-old crioulo broodmare at one day postpartum presented signs of difficulty to walk, positive pulse in the four limbs, and heart rate of 80 beats per minute (bpm), with a history of fighting with another mare. The clinical suspicions were rhabdomyolysis and laminitis. Initially a dose of flunixin meglumine was administrated intravenous to prevent an endotoxemia. On the same day, the blood collection showed an elevated number of white blood cells, predominantly neutrophils and monocytes. An antimicrobial treatment with ceftiofur hydrochloride at a dose of 2.2 mg/kg intramuscular was applied. At the first day, the mare does not show signs of drug side effect. However, 24 hours later, in the second application, the patient presents incoordination, dizziness, and loss of equilibrium. At the same time, dexamethasone was administrated. The signs were reverted, and the mare was normal after the reaction. The treatment with ceftiofur was changed to enrofloxacin, and the animal had a complete recovery. These drug reactions are not common in the routine of equine clinical practitioners, but they cause a great preoccupation for the owner and the veterinarian.<br />
DOI: 10.1016/j.jevs.2020.103295 PMID: 33276911 [Indexed for MEDLINE]<br />
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[5]. Chem Pharm Bull (Tokyo). 2020 Nov 1;68(11):1061-1068. doi: 10.1248/cpb.c20-00483. Epub 2020 Sep 4.<br />
Acute Oral Toxicity and Acute Intraperitoneal Studies of Thermally Treated Ceftiofur.<br />
Zhang H(1), Lu S(1), Ren H(1), Zhao K(1), Li Y(1), Guan Y(1), Li H(1), Zheng Y(1), Hu P(1), Liu Z(1).<br />
Author information: (1)Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University.<br />
Ceftiofur (CEF) is a third-generation and the first animal-specific cephalosporin that is widely used in animal husbandry. As a heat-labile antibiotic, the cytotoxicity of CEF after thermal treatment has been reported. This study seeks to investigate the potential toxicity of thermally treated CEF (TTC) in vivo based on acute oral toxicity studies and acute intraperitoneal studies in mice. Our data indicated that TTC exhibited significant increased toxicity in mice compared with CEF. TTC resulted in weight gain, hypercholesterolemia, hepatocyte steatosis and hepatocyte mitochondrial damage, and downregulated β-oxidation-related genes in mice in acute oral toxicity studies. In addition, TTC caused acute pulmonary congestion, increased levels of reactive oxygen species (ROS), prolonged coagulation time, and even death in mice in acute intraperitoneal toxicity studies. Our data showed that thermal treatment enhanced the toxicity of CEF in vivo. Lung and liver are the main target organs in the pathological damage process mediated by TTC. These findings suggested that residual CEF in animal-derived food may represent a potential food safety risk and pose a potential threat to human health.<br />
DOI: 10.1248/cpb.c20-00483 PMID: 32893223 [Indexed for MEDLINE]
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