摘要
为研究氟苯尼考在鲫和草鱼体内的药代学、药效动力学联合参数,并制定氟苯尼考对鲫、草鱼的精确用药方案,本实验结合氟苯尼考对致病性嗜水气单胞菌CAAh01的体外药效学研究和口灌不同剂量的氟苯尼考在鲫、草鱼体内药代动力学研究,确定了氟苯尼考防治该致病菌引起的鲫和草鱼细菌性败血症的给药方案。研究结果显示,氟苯尼考对CAAh01菌株的最小抑菌浓度（MIC）为0.5μg/mL,最小杀菌浓度（MBC）为1.0μg/mL,防细菌耐药突变浓度（MPC）为6.0μg/mL,防耐药突变选择窗（MSW）为0.5~6.0μg/mL。按10、20、30 mg/kg体质量剂量对鲫、草鱼口灌氟苯尼考后,在鲫体内,血药浓度大于MPC的维持时间分别为5、8、24 h;AUC24/MIC分别为177.06、265.90、426.50;Cmax/MIC分别为15.59、21.32、31.24。在草鱼体内,血药浓度大于MPC的维持时间分别为0、0、3 h;AUC24/MIC分别为38.60、75.08、121.94;Cmax/MIC分别为4.75、10.08、19.99。研究表明,综合血药浓度维持MPC以上的时间、AUC24/MIC或Cmax/MIC指标,氟苯尼考适用于鲫细菌性疾病的防治,其防突变用药方案为剂量30 mg/kg,每日1次给药,休药期不低于20 d。对于草鱼细菌性疾病的防治,氟苯尼考不宜连续使用。
This study aims to investigate the differences of in vitro pharmacodynamics（ PD） parameters and in vivo pharmacokinetic（ PK） of florfenicol in crucian carp（ Carassius auratus） and grass carp（ Ctenopharyngodon idella） against a pathogenic Aeromonas hydrophila strain（ CAAh01）,which were used to draw reasonable medication regimen to control disease and prevent drug resistant bacteria. The pharmacodynamics of florfenicol on bacterium CAAh01 were studied in vitro and the pharmacokinetic parameters of florfenicol in crucian carp and grass carp were monitored after a single oral gavage of 10,20,30 mg per kg body weight to determine a medication regimen to prevent bacterial sepsis in grass carp and crucian carp. The in vitro pharmacodynamic results showed that MIC of florfenicol on CAAh01 was 0. 5 μg /mL,and MBC was 1. 0 μg /mL; the MPC was 6. 0 μg /mL（ 12MIC）; the mutant selection window（ MSW）of florfenicol on the pathogenic bacterial strains was 0. 5-6. 0 μg /mL. The time of florfenicol concentration in serum of crucian carp above MPC was 5h at the dosage of 10 mg /kg; 8 h at the dosage of 20 mg /kg,24 h at the dosage of 30 mg /kg,respectively; AUC24/MIC and Cmax/MIC of florfenicol in serum were177. 06 and 15. 59 at the dosage of 10 mg /kg,respectively; 265. 90 and 21. 32 at the dosage of 20 mg /kg,respectively; 426. 50 and 31. 24 at the dosage of 30 mg /kg,respectively. The time of florfenicol concentration in serum of grass carp above MPC was 0h at the dosage of 10 mg /kg and 20 mg /kg,3h at the dosage of 30 mg /kg,respectively; AUC24/MIC and Cmax/MIC of florfenicol in serum were 38. 60 and 4. 75at the dosage of 10 mg /kg,respectively; 75. 08 and 10. 08 at the dosage of 20 mg /kg,respectively; 121. 94and 19. 99 at the dosage of 30 mg /kg,respectively. Considering the drug remained in the plasma with a concentration above MPC and AUC24 /MIC ≥ 100 or Cmax/MIC ＆gt; 8,florfenicol is determined to be applicable for the prevention and treatment of bacterial diseases of crucian carp. The recommendation of the dosing regimen to prevent the selection of drug-resistance is 30 mg /kg,at the intervals of 24 h for 1 day,and the proposed withdrawal period should not be less than 20 d. However,it is not suitable to be used continuously to control and treat bacterial diseases in grass garp.
出处
《水产学报》
CAS
CSCD
北大核心
2014年第6期888-895,共8页
Journal of Fisheries of China
基金
现代农业产业技术体系建设专项(CARS-46-12)
关键词
鲫
草鱼
氟苯尼考
嗜水气单胞菌
防耐药突变浓度
药代动力学
药效动力学
Carassius auratus
Ctenopharyngodon idella
florfenicol
Aeromonas hydrophila
mutant prevention concentration
pharmacodynamics
pharmacokinetic
