Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2022.975113/full |
| _version_ | 1798000559904522240 |
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| author | Anna Catherine Bowden Rachel A. Allbaugh Joe S. Smith Jonathan P. Mochel Lionel Sebbag Lionel Sebbag Lionel Sebbag |
| author_facet | Anna Catherine Bowden Rachel A. Allbaugh Joe S. Smith Jonathan P. Mochel Lionel Sebbag Lionel Sebbag Lionel Sebbag |
| author_sort | Anna Catherine Bowden |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T11:22:15Z |
| format | Article |
| id | doaj.art-036dd6e37bc94155b3a766154baf8b2a |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-04-11T11:22:15Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-036dd6e37bc94155b3a766154baf8b2a2022-12-22T04:26:45ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692022-09-01910.3389/fvets.2022.975113975113Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogsAnna Catherine Bowden0Rachel A. Allbaugh1Joe S. Smith2Jonathan P. Mochel3Lionel Sebbag4Lionel Sebbag5Lionel Sebbag6Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesDepartment of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United StatesKoret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, IsraelPurposeDescribe 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.https://www.frontiersin.org/articles/10.3389/fvets.2022.975113/fullbacterial keratitisantibiotictear filmcaninePK-PDblood tear barrier |
| spellingShingle | Anna Catherine Bowden Rachel A. Allbaugh Joe S. Smith Jonathan P. Mochel Lionel Sebbag Lionel Sebbag Lionel Sebbag Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs Frontiers in Veterinary Science bacterial keratitis antibiotic tear film canine PK-PD blood tear barrier |
| title | Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs |
| title_full | Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs |
| title_fullStr | Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs |
| title_full_unstemmed | Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs |
| title_short | Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede®) in dogs |
| title_sort | kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended release parenteral administration excede r in dogs |
| topic | bacterial keratitis antibiotic tear film canine PK-PD blood tear barrier |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2022.975113/full |
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