人工海水浸泡致低体温比格犬体内左氧氟沙星的药动学研究  

Pharmacokinetics of Levofloxacin in Hypothermic Beagle Dogs by Artificial Seawater Immersion

作　　者：张沂[1] 王强[1] 尚利群[2] 虞积耀[3] 王大鹏[3] 任婷麟[1] 于春令[1] 邸秀珍[1] 

机构地区：[1]海军总医院药剂科,北京100037 [2]海军总医院胸外科,北京100037 [3]海军总医院海战伤救治研究中心,北京100037

出　　处：《中国药学杂志》2009年第18期1409-1412,共4页Chinese Pharmaceutical Journal

基　　金：全军医药卫生科研基金课题(06D004)

摘　　要：目的建立海水浸泡致低体温比格犬动物模型,研究并比较左氧氟沙星在低体温比格犬动物模型中及正常体温比格犬中的药动学。方法8只比格犬随机分为2组,每组4只。组1为正常组,组2为低体温动物模型组。组2比格犬于海水池中浸泡90min后移出。2组动物给药方案为:左氧氟沙星25mg·kg-1,静脉输注,60min输注完毕。采用HPLC测定左氧氟沙星血药浓度;3P97程序计算药动学参数;SPSS程序进行统计学处理;同时连续监测实验动物体温。结果组1动物体温给药前及给药后24,72h体温分别为(37.30±0.38),(37.10±0.26)和(37.18±0.17)℃;组2动物海水浸泡前体温为(37.70±1.41)℃,海水浸泡45,90min、出水后1,4,12,24,48及72h体温分别为(36.33±0.21),(34.45±0.46),(30.13±1.41),(32.95±2.29),(35.30±0.59),(35.70±0.55),(36.4±0.46)和(37.30±0.38)℃。左氧氟沙星在2组动物中药动学呈二房室模型,组1和组2药动学参数分别为:ρmax(30.05±1.75)和(44.56±11.63)mg·L-1,t1/2β(8.23±0.65)和(13.69±1.78)h,AUC(247.00±14.10)和(389.79±103.14)mg·h·L-1,Vc(7.47±3.13)和(7.14±2.53)L,CLS(1.20±0.15)和(1.0±0.33)L·h-1。统计学处理结果显示,药动学参数t1/2β,AUC组间具有显著性差异(P<0.05)。结论海水浸泡致低体温条件下,左氧氟沙星在比格犬中的药动学特性发生显著变化,其消除半衰期较体温正常组延长,药-时曲线下面积增加。OBJECTIVE To compare the pharmacokinetics of levofloxacin （LVFX） between hypothermic animal and healthy animal by establishing hypothermic animal model. METHODS Eight healthy beagle dogs were randomly divided into control group （group 1, n=4） and model group （group 2, n=4）. Group 1 were administered a single intravenous dose of LVFX （25 mg·kg^-1） by infusion into saphenous vein. Group 2 was administered after seawater immersion 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 program. RESULTS The temperature of animal in group 1 before and at 24, 72 h postdose were （37.30±0.38）, （37.10±0.26） and （37.18±0.17） ℃, respectively, and those in group 2 were （37.70± 1.41） ℃ at before immersion, （36.33±0.21） and （34.45±0.46）℃ at 45, 90 min alter immersion process, （30.13±1.41）, （32.95±2.29）, （35.30±0.59）, （35.70±0.55）, （36.4±0.46） and （37.30±0.38）℃ at 1, 2, 4, 12, 24, 48 and 72 h after administration respectively. When LVFX was intravenously administered by infusion, the plasma concentration-time curve of two groups were both fit to a two-compartment model with the main pharmacokinetic parameters as follows： ρmax （30.05±1.75） and （44.56±11.63） mg·L^-1, t1/2β （8.23±0.65） and （13.69±1.78） h, AUC （247.00±14.10） and （389.79±103.14） mg·h·L^-1, Vc （7.47±3.13） and （7.14±2.53） L, CLs （1.20±0.15） and （1.0±0.33） L·h^-1, respectively. And there were significantly different in t1/2βand AUC between group 1 and group 2 （P〈0.05） . CONCLUSION Hypothermia by seawater immersion has significantly effect on the pharmacokinetics of LVFX in beagle dogs. Compared with control group, t1/2β and AUC of hypothermic beagle dog were both increased significantly.

关 键 词：左氧氟沙星 药动学 人工海水浸泡 低体温 比格犬 

分 类 号：R969[医药卫生—药理学]