不同海水浸泡时间对左氧氟沙星在腹部开放伤比格犬体内的药动学影响

目的建立腹部开放性创伤合并海水浸泡比格犬动物模型,研究左氧氟沙星（LVFX）在腹部开放性损伤合并海水浸泡比格犬与正常比格犬中的药动学变化。方法 12只比格犬随机分为3组,每组4只。A组为正常对照组,B组为腹部开放性创伤合并海水浸泡45 min组,C组为腹部开放性创伤合并海水浸泡90 min组。3组动物给药方案为：静脉输注LVFX25 mg/kg,60 min输注完毕。实验进程中监测实验动物体温。采用HPLC测定LVFX浓度;3P97计算药动学参数。结果腹部开放性创伤合并海水浸泡比格犬在浸泡过程中和出水后体温显著下降,且随浸泡时间增加而下降幅度增加。LVFX在比格犬体内呈二室模型,A、B和C组药动学参数分别为：Cmax（30.05±1.75）、（36.10±4.74）和（42.34±4.19）mg/L,t1/2β（8.23±0.65）、（11.02±0.54）和（13.19±3.87）h,AUC（247.00±14.10）、（345.22±56.68）和（417.79±83.32）mgoh/L,Vc（6.97±2.02）、（6.68±1.67）和（7.82±1.62）L,ClS（1.20±0.15）、（1.06±0.12）和（0.92±0.15）L/h。与A组比较,B组t1/2β和AUC显著增加（P〈0.05）;C组t1/2β、Cmax和AUC（t1/2β,P〈0.01;Cmax,AUC,P〈0.05）显著增加。与B组比较,C组t1/2β（P〈0.05）差异明显。结论腹部开放性创伤合并海水浸泡比格犬体内LVFX代谢消除随浸泡时间延长而明显减慢,其机制可能与浸泡导致的低体温状况有关。

Pharmacokinetics of levofloxacin in beagle dogs with open abdominal wound by different seawater immersion process

Objective To compare the pharmacokinetics of levofloxacin（LVFX） between beagle dogs with open abdominal wound by seawater immersion for different time and normal dogs.Methods Twelve healthy beagle dogs were randomly divided into control group（A group,n=4）,open abdominal wound and immersion for 45 min group（B group,n=4） and open abdominal wound and immersion for 90 min group（C group,n=4）.The beagle dogs in B group and C group were immersed into artificial seawater for 45 or 90 min before administered,respectively.All the animal were administered a single dose of LVFX（25 mg/kg） by infusion into saphenous vein for 90 min.LVFX in plasma at different sampling time was determined by HPLC,at the same time,the temperature of animal was monitored.The pharmacokinetic parameters were calculated by 3P97 software and examined by SPSS 12.1 program.Results The temperature of animal in B and C group dropped significantly compared with A group in immersion process and after immersion,and these drops temperature were increased along with the extension of immersion process.The plasma concentration-time curve of three groups were fit to a two-compartment model with the main pharmacokinetic parameters as follows： Cmax were（30.05±1.75）,（36.10±4.74）and（42.34±4.19） mg/ L,t1/2β were（8.23±0.65）,（11.02±0.54） and（13.19±3.87） h,AUC were（247.00±14.10）,（345.22±56.68） and（417.79± 83.32） mgoh/ L,Vc（6.97±2.02）,（6.68±1.67） and（7.82±1.62） L,ClS（1.20±0.15）,（1.06±0.12） and（0.92±0.15） L/ h,respectively.In comparison to A group,t1/2β and AUC of B group was increased remarkably（P0.05,respectively）,and t1/2β,Cmax and AUC of C group was also increased remarkably,respectively.（t1/2β,P0.01;Cmax,AUC,P0.05）.At the same time,there was sinificantly difference in t1/2β between B group and C group（P0.05）.Conclusion Metabolism and elimination of LVFX in open abdominal wound by seawater immersion was obviously decreased when the immersion process was increased,and hypothermia in beagle that immersion led to might be invovled in these events.