Pharmacokinetic profile and effect on the faecal microbiome of a single dose of pradofloxacin oral suspension in the rabbit (Oryctolagus cuniculus)

被引:2
作者
Xie, Shangzhe [1 ,2 ]
Trott, Darren J. [2 ]
Saputra, Sugiyono [2 ]
Ebrahimie, Esmaeil [2 ,3 ]
Dehcheshmeh, Manijeh Mohammadi [2 ]
Page, Caitlyn [2 ]
Woodward, Nicola [2 ]
Griffiths, Neil [2 ]
Kimble, Benjamin [4 ]
Govendir, Merran [4 ]
机构
[1] Mandai Wildlife Grp, Singapore, Singapore
[2] Univ Adelaide, Australian Ctr Antimicrobial Resistance Ecol, Sch Anim & Vet Sci, Roseworthy Campus, Roseworthy, SA, Australia
[3] La Trobe Univ, Coll Sci Hlth & Engn, Sch Life Sci, La Trobe Genom Res Platform, Melbourne, Vic, Australia
[4] Univ Sydney, Sydney Sch Vet Sci, Sydney, NSW, Australia
基金
澳大利亚研究理事会;
关键词
antibiotics; microbiome; pharmacokinetics; pradofloxacin; rabbits; PHARMACODYNAMIC INTEGRATION; PROTEOBACTERIA; MARBOFLOXACIN; ENROFLOXACIN; ORBIFLOXACIN; SIGNATURE; BACTERIA; DOGS;
D O I
10.1111/jvp.13038
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Fluoroquinolones are often administered to pet rabbits given their perceived safety and limited effects on anaerobic gut microbiota. However, the pharmacokinetics and relative safety of pradofloxacin, a third-generation veterinary fluoroquinolone with a much broader spectrum of activity, have not been reported in this species. Here, we determined the pharmacokinetic profile of a single dose of oral pradofloxacin in rabbits and evaluated effects on the faecal microbiome. Four mature female rabbits were administered pradofloxacin (25 mg/ml oral suspension), at a dose of 7.5 mg/kg. The pradofloxacin median (range) T-max was 4.50 (2.00-5.00) h, C-max 600.66 (395.85-886.72) ng/ml and t(1/2) was 1.27 (0.12-1.39) h. These results indicated that oral absorption of pradofloxacin was slower, and elimination faster compared with other fluoroquinolones in healthy rabbits, as well as relative to cats and dogs. Following treatment with pradofloxacin, faecal microbiota profiling showed some compositional differences between treated and control animals. This was the result of a significant decrease in the abundance of Proteobacteria, in particular bacteria belonging to the Pseudomonas, Atopostipes and Parabacteroides genera. The pharmacokinetic profile of pradofloxacin in rabbits should be further studied by increasing the sample size and using multiple-dose protocols (i.e. 7 days) to confirm safety. Further information on the effects of protein binding, higher dosages and disease on pradofloxacin pharmacokinetics in rabbits are needed before an accurate dosing regimen can be recommended.
引用
收藏
页码:203 / 212
页数:10
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