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

张沂 ;王强 ;尚利群 ;虞积耀 c;王大鹏 c;任婷麟 ;于春令 ;邸秀珍

中国药学杂志 ›› 2009, Vol. 44 ›› Issue (18) : 1409-1411.

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中国药学杂志 ›› 2009, Vol. 44 ›› Issue (18) : 1409-1411.
论文

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

  • 张沂 a ,王强 a ,尚利群 b ,虞积耀 c ,王大鹏 c ,任婷麟 a ,于春令 a ,邸秀珍 a
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Pharmacokinetics of Levo floxacin in Hypothermic Beagle Dogs by Artificial Seawater Immersion

  • ZHANG Yia , WANG Qianga , SHANG Li-qunb , YU Ji-yaoc , WANG Da-pengc , REN Ting-lina , YU Cun-ling a , DI Xiu-zhen a
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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 90 min 后移出。 2 组动物给药方案为:左氧氟沙星 25 mg·kg-1 ,静脉输注, 60 min 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 , 72 h 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 , 90 min 、出水后 1 , 4 , 12 , 24 , 48 及 72 h 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: <> ρ max ( 30.05±1.75 )和( 44.56±11.63 ) mg·L-1 t 1/2β ( 8.23±0.65 )和( 13.69±1.78 ) h , AUC ( 247.00±14.10 )和( 389.79±103.14 ) mg·h·L-1 V c ( 7.47 ± 3.13 )和( 7.14 ± 2.53 ) L , CL S ( 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 t 1/2β , 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。

Abstract

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 after 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 t1/2β and 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. style="width:400px" rows="8" cols="">

关键词

左氧氟沙星 / 药动学 / 人工海水浸泡 / 低体温 / 比格犬

Key words

levofloxacin / pharmacokinetics / artificial seawater immersion

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导出引用
张沂 ;王强 ;尚利群 ;虞积耀 c;王大鹏 c;任婷麟 ;于春令 ;邸秀珍 . 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[J]. 中国药学杂志, 2009, 44(18): 1409-1411
ZHNG Yi;WNG Qing;SHNG Li-qun;YU Ji-yoc;WNG D-pengc;REN Ting-lin;YU Cun-ling;DI Xiu-zhen . Pharmacokinetics of Levo floxacin in Hypothermic Beagle Dogs by Artificial Seawater Immersion[J]. Chinese Pharmaceutical Journal, 2009, 44(18): 1409-1411

参考文献


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( 收稿日期 : 2009-05-06 )


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