Bowden Anna Catherine, Allbaugh Rachel A, Smith Joe S, Mochel Jonathan P, Sebbag Lionel
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Department of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Front Vet Sci. 2022 Sep 20;9:975113. doi: 10.3389/fvets.2022.975113. eCollection 2022.
Describe 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.
Six 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 and by assessing bacterial growth ( = 10 per bacterial species) in the presence of ceftiofur at increasing concentrations.
Blood-tear barrier breakdown provided tear film concentrations of ceftiofur 3.2-28.9-fold higher than in the contralateral healthy eye ( = 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).
Ceftiofur 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.
描述长效胃肠外注射头孢噻呋（Excede）在犬泪膜中的药代动力学，并将这些浓度与头孢噻呋对犬常见眼部病原体的最低抑菌浓度（MICs）进行比较。
纳入6只不同品种的犬。通过组胺诱导的结膜炎破坏血 - 泪屏障，以确保结果具有临床相关性。每只犬皮下注射5mg/kg的Excede一次，然后在0、0.25、0.5、1、2、4、8、12、24、36、48、72、96、120、144、168、192、216和240小时用Schirmer试纸收集眼泪。采用液相色谱 - 质谱法进行药物定量。通过评估在浓度不断增加的头孢噻呋存在下细菌的生长情况（每个细菌种类 = 10）来测定 和 的MICs。
血 - 泪屏障破坏后，泪膜中头孢噻呋的浓度比健侧眼高3.2 - 28.9倍（ = 1只犬，预实验）。在所有6只犬中，眼泪中头孢噻呋的浓度在2.3至637.5 ng/mL之间变化，皮下注射后长达10天（240小时）均可检测到。然而，眼泪中的浓度始终低于常见眼部分离株的MICs（≥640 ng/mL）。
单次胃肠外注射后，头孢噻呋可进入泪腔（长达10天），但眼泪中的浓度变化极大且过低，无法有效对抗犬常见的细菌病原体。有必要对不同的头孢噻呋剂量或其他长效注射用抗生素进行进一步研究。
