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Plasma and pulmonary pharmacokinetics of desfuroylceftiofur acetamide after weekly administration of ceftiofur crystalline free acid to adult horses
Author(s) -
Fultz L.,
Giguère S.,
Berghaus L. J.,
Davis J. L.
Publication year - 2014
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12107
Subject(s) - medicine , pharmacokinetics , horse , regimen , pleuropneumonia , ceftiofur , pharmacology , antibiotics , chemistry , biology , cephalosporin , paleontology , biochemistry , radiology
Summary 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 D ay 0, D ay 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.