Pulmonary pharmacokinetics of desfuroylceftiofur acetamide after nebulisation or intramuscular administration of ceftiofur sodium to weanling foals.

REASONS FOR PERFORMING STUDY: Administration of ceftiofur sodium via nebulisation has been recommended for the treatment of bronchopneumonia in horses, despite the lack of pharmacokinetic and safety data. OBJECTIVES: To compare concentrations of desfuroylceftiofur acetamide (DCA) in plasma and pulmonary epithelial lining fluid (PELF) of foals after nebulisation or i.m. administration of ceftiofur sodium and to determine if nebulisation of ceftiofur sodium induces airway inflammation. STUDY DESIGN: Randomised experimental study. METHODS: Six weanling foals received ceftiofur sodium (2.2 mg/kg bwt daily for 5 doses) by the i.m. route and 6 foals received the same dose by nebulisation. Concentrations of DCA in plasma and PELF were measured after Doses 1 and 5, and differential cell counts were performed on bronchoalveolar lavage samples obtained after Dose 5. RESULTS: Foals receiving ceftiofur sodium via nebulisation had significantly lower peak concentrations (0.15 ± 0.12 vs. 6.15 ± 0.75 mg/l) and area under the curve (1.26 ± 0.96 vs. 37.63 ± 4.01 mg●h/l) in plasma compared with those receiving the drug by the i.m. route. In contrast, foals receiving ceftiofur sodium via nebulisation had significantly higher peak concentrations (4.52 ± 2.91 vs. 0.73 ± 0.73 mg/l) and area under the curve (24.14 ± 14.09 vs. 5.91 ± 3.28 mg●h/l) in PELF compared with those receiving the drug by the i.m. route. Cell concentration and differential cell count in bronchoalveolar lavage fluid of foals nebulised with ceftiofur sodium were not significantly different from those of foals nebulised with saline. CONCLUSIONS: Administration of ceftiofur sodium via nebulisation is well tolerated and DCA concentrations in PELF remain above the minimum inhibitory concentration of the drug required to inhibit the growth of 90% of Streptococcus zooepidemicus for approximately 24 h after administration. Nebulised ceftiofur sodium warrants further investigation for the treatment of bacterial infections of the lower respiratory tract in horses.

Plasma and pulmonary pharmacokinetics of desfuroylceftiofur acetamide after weekly administration of ceftiofur crystalline free acid to adult horses.

REASONS FOR PERFORMING STUDY: Current labelling for the use of ceftiofur crystalline free acid (CCFA) in horses states that 2 i.m. doses must be administered 4 days apart to provide 10 days of therapeutic coverage. A 10 day treatment regimen is not sufficient for the long-term treatment of horses with severe lung consolidation or pleuropneumonia. There are currently no data to guide an appropriate dosing interval when a longer treatment regimen is warranted. OBJECTIVES: To determine steady-state plasma and pulmonary epithelial lining fluid (PELF) concentrations of desfuroylceftiofur acetamide (DCA) after weekly i.m. administration of CCFA to adult horses. STUDY DESIGN: Experimental study. METHODS: Seven adult horses received i.m. CCFA at a dose of 6.6 mg/kg bwt on Day 0, Day 4 and every 7 days thereafter for 3 additional doses. Concentrations of DCA in plasma and PELF were measured at various time intervals. RESULTS: After weekly i.m. administration, the mean (± s.d.) steady-state peak DCA concentration in plasma (2.87 ± 1.50 µg/ml) was significantly higher than that in PELF (0.84 ± 0.53 µg/ml). Mean terminal half-lives in plasma (77.5 ± 17.5 h) and PELF (92.8 ± 59.0 h) were not significantly different. Concentrations of DCA in plasma and PELF remained in the therapeutic range for the entire dosing interval. CONCLUSIONS: After the initial 2-dose regimen 4 days apart, weekly i.m. administration of CCFA was well tolerated and resulted in plasma and PELF DCA concentrations above the minimal inhibitory concentration that inhibits growth of at least 90% of common lower respiratory tract pathogens of horses. POTENTIAL RELEVANCE: Weekly administration of CCFA would appear appropriate when a treatment regimen longer than 10 days is warranted based on clinical signs and disease severity.