Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs

Abstract

PurposeDescribe the pharmacokinetics of extended-release parenteral ceftiofur (Excede®) in canine tear film and compare these concentrations to minimal inhibitory concentrations (MICs) of ceftiofur against common ocular pathogens in dogs.MethodSix dogs of various breeds were enrolled. Disruption of blood-tear barrier was achieved with histamine-induced conjunctivitis to ensure clinical relevance of the results. Each dog received a single subcutaneous injection of 5 mg/kg Excede®, followed by tear collection with Schirmer strips at times 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 h. Drug quantification was performed with liquid chromatography-mass spectrometry. MICs were determined for Staphylococcus pseudintermedius, Streptococcus canis and Pseudomonas aeruginosa by assessing bacterial growth (n = 10 per bacterial species) in the presence of ceftiofur at increasing concentrations.ResultsBlood-tear barrier breakdown provided tear film concentrations of ceftiofur 3.2–28.9-fold higher than in the contralateral healthy eye (n = 1 dog, pilot experiment). In all six dogs, ceftiofur concentrations in tears varied from 2.3 to 637.5 ng/mL and were detectable up to 10 days (240 h) after subcutaneous injection. However, tear levels always remained below MICs for common ocular isolates (≥640 ng/mL).ConclusionsCeftiofur reached the tear compartment (for up to 10 days) after a single parenteral injection, however tear concentrations were extremely variable and too low to be effective against common bacterial pathogens in dogs. Further studies with different ceftiofur dosage or other long-acting injectable antibiotics are warranted.

Systemic absorption and gastrointestinal adverse effects from topical ketorolac and diclofenac ophthalmic solutions in healthy dogs

“…Indeed, canine eyes with various pathologies requiring topical NSAIDs (eg, conjunctivitis, uveitis, cataracts) are known to have "leaky" conjunctiva, that is, a breakdown of the blood-tear barrier that might allow tear film compounds to reach the systemic circulation at higher levels and vice versa. 25,[32][33][34][35] Finally, the small sample size must be taken into consideration when interpreting the statistical relationship found between endoscopic scores and plasma ketorolac concentrations.…”

Progressive ulcerative keratitis in dogs in the United Kingdom: Microbial isolates, antimicrobial sensitivity, and resistance patterns

“…While systemic antimicrobials have been detected in the tear film following systemic administration, 68,69 Collins et al 70 . and Bowden et al 71 . concluded that the achieved concentrations of doxycycline and ceftiofur, respectively, in the canine tear film were too low for any effective antimicrobial effect.…”

“…19,20,23,24 We show treating infected corneal ulcers with a systemic antimicrobial had no effect on whether an infected ulcer tested positive or not. While systemic antimicrobials have been detected in the tear film following systemic administration, 68,69 Collins et al 70 and Bowden et al 71 concluded that the achieved concentrations of doxycycline and ceftiofur, respectively, in the canine tear film were too low for any effective antimicrobial effect. Oral doxycycline administration could instead have a positive effect on ulcer healing by inhibiting the matrix metalloproteinases responsible for corneal degradation but randomized and masked clinical trials are necessary to confirm its benefit.…”