【摘要】 目的探讨喹诺酮类药物对茶碱药代动力学是否存在显著影响,为临床合理用药提供参考。方法采用自身对照法,测定家兔iv 10mg.kg-1茶碱及每天1次灌服喹诺酮类药物,连续6d,再iv 10mg.kg-1茶碱后血浆中茶碱浓度,计算药动学参数。结果合用氟罗沙星前后茶碱在家兔体内按一室模型处理。合用前后茶碱的的药动学参数分别为,K:0.154±0.035h-1,0.151±0.044 h-1;T1/2:4.70±1.12 h,4.90±1.38 h;V:0.562±0.180 L.kg-1,0.556±0.166 L.kg-1;AUC0~10:93.70±32.87 mg.h.L-1,100.20±43.11 mg.h.L-1;AUC0~∞:147.87±68.08 mg.h.L-1,157.16±80.69 mg.h.L-1;CL:0.090±0.046 L.kg-1.h-1,0.091±0.052 L.kg-1.h-1;Cm ax:19.91±5.25 mg.L-1,20.12±5.24 mg.L-1。以上合参数均无显著性差异(P>0.05)。合用氟罗沙星后茶碱的血浆浓度有一定波动,但无统计学意义(P>0.05)。合用芦氟沙星前后茶碱在家兔体内呈一室模型。茶碱的药动学参数分别为,K:0.147±0.017 h-1,0.148±0.018 h-1;T1/2:4.76±0.54 h,4.74±0.56 h;V:0.581±0.089 L.kg-1,0.555±0.075 L.kg-1;AUC0~10:91.42±11.14 mg.h.L-1,94.97±10.20mg.h.L-1;AUC0~∞:119.48±14.96 mg.h.L-1,124.05±14.76 mg.h.L-1;CL:0.085±0.011 L.kg-1.h-1,0.082±0.010L.kg-1.h-1;Cmax:18.48±2.53 mg.L-1,19.16±2.34mg.L-1。合用芦氟沙星前后茶碱各参数均无显著性差异(P>0.05)。合用芦氟沙星后茶碱的血浆浓度有升高趋势,但无统计学意义(P>0.05)。合用培氟沙星前后茶碱在家兔体内呈一室模型。茶碱的药动学参数分别为,K:0.150±0.038 h-1,0.110±0.018 h-1,P<0.01;T1/2:4.95±1.67 h,6.69±2.01 h,P<0.01;V:0.584±0.149 L.kg-1,0.511±0.126 L.kg-1,P<0.05;AΜC0~10:97.71±40.09 mg.h.L-1,126.11±42.72 mg.h.L-1,P<0.01;AΜC0~∞:136.05±83.40 mg.h.L-1,202.10±99.81 mg.h.L-1,P<0.01;CL:0.091±0.038 L.kg-1.h-1,0.056±0.018 L.kg-1.h-1,P<0.01;Cmax:18.94±4.89 mg.L-1,21.82±5.40 mg.L-1,P<0.05。合用加替沙星前后茶碱在家兔体内按一室模型处理。合用前后茶碱的药动学参数分别为,K:0.147±0.035 h-1,0.127±0.026 h-1;T1/2:4.89±0.98 h,5.62±1.09h;V:0.541±0.162 L.kg-1,0.538±0.154 L.kg-1;AΜC0~10:97.81±29.87 mg.h.L-1,107.27±39.54mg.h.L-1;AΜC0~∞:153.32±65.64 mg.h.L-1,174.01±71.03 mg.h.L-1;CL:0.081±0.034 mg.h.L-1,0.074±0.033 L.kg-1.h-1;Cmax:20.51±5.12 mg.L-1,20.60±5.05 mg.L-1。合用加替沙星前后茶碱各参数除T1/2(P<0.05)外无显著差异。结论氟罗沙星、芦氟沙星对茶碱的血药浓度及药代动学参数没有显著影响;培氟沙星对茶碱的血药浓度及药代动学参数有显著影响;加替沙星对茶碱的血药浓度及除T1/2的药代动学参数没有显著影响。更多还原

【Abstract】 OBJECTIVE To investigate whether quinolones may influence theophylline pharmacokinetic parameters.METHODS In self-control desing,the plasma concentrations of theophylline were determined after intravenous dose 10mg·kg^-1 of theophylline alone,followed by oral administration of quinolones,once daily for 6 days,and determination of the plasma concentrations of theophylline after intravenous dose 10mg·kg^-1 of theophylline again at the 6^th day.The pharmacokinetic parameters of theophylline were estimated. RESULTS The pharmacokinetics of theophylline used alone and coadministered with fleroxacin was fit to one compartment model.The pharmacokinetics parameters of theophylline used alone and coadministered with fleroxacin is as follows:K:0.154±0.035 h^-1,0.151±0.044 h^-1;T_1/2:4.70±1.12 h,4.90±1.38 h;V:0.562±0.180 L·kg^-1,0.556±0.166 L·kg^-1;AUC_0～10:93.70±32.87 mg·h·L^-1,100.20±43.11 mg·h·L^-1;AUC_0～∞:147.87±68.08 mg·h·L^-1,157.16±80.69 mg·h·L^-1;CL:（0.090）±0.046 L· kg^-1·h^-1,0.091±0.052 L·kg^-1·h¹;Cmax:19.91±5.25 mg·L^-1,20.12±5.24 mg·L^-1.The study suggests that fleroxacin had minor influence on pharmacokinetics of theophylline in rabbits.The two drugs can be administered concurrently.The pharmacokinetics of theophylline used alone and coadministered with rufloxacin was fit to one compartment model.The pharmacokinetics parameters of theophylline used alone and coadministered with rufloxacin is as follows: K: 0.147±0.017 h^-1,0.148±（0.018） h^-1;T_1/2:4.76±0.54 h,4.74±0.56 h;V:0.581±0.089 L·kg^-1,0.555±0.075 L·kg^-1;AUC_0～10:91.42±11.14 mg·h·L^-1,94.97±10.20mg·h·L^-1;AUC_0～∞:119.48±14.96 mg·h·L^-1,124.05±14.76 mg·h·L^-1;CL :0.085±0.011 L·kg^-1·h^-1,0.082±0.010L·kg^-1·h^-1;Cmax:18.48±2.53 mg·L^-1,19.16±2.34mg·L^-1.The study suggests that rufloxacin had minor influence on pharmacokinetics of theophylline in rabbits.The pharmacokinetics of theophylline used alone and coadministered with pefloxacin was fit to one compartment model.The pharmacokinetic parameters of theophylline used alone and coadministered with pefloxacin is as follows : K: 0.150±0.038 h^-1,0.110±0.018 h^-1,P<0.01;T_1/2:4.95±1.67 h,6.69±2.01 h,P<0.01;V:（0.584）±0.149 L·kg^-1,0.511±0.126 L· kg^-1,P<0.05;AΜC_0～10:97.71±40.09 mg·h·L^-1,126.11±42.72 mg·h·L^-1,P<0.01;AΜC_0～∞:136.05±83.40 mg·h·L^-1,202.10±99.81 mg·h·L^-1,P<0.01;CL:0.091±0.038 L·kg^-1·h^-1,（0.056）±0.018 L·kg^-1·h^-1,P<0.01;Cmax:18.94±4.89 mg·L^-1,21.82±5.40 mg·L^-1,P<0.05.There were statistical significance between pharmacokinetic parameters of theophylline used alone and coadministered with pefloxacin.The pharmacokinetics of theophylline used alone and coadministered with gatifloxacin was fit to one compartment model.The pharmacokinetic parameters of theophylline used alone and coadministered with gatifloxacin is as follows: K:0.147±0.035 h^-1,0.127±0.026 h^-1;T_1/2:4.89±（0.98） h,5.62±1.09h;V:0.541±0.162 L· kg^-1,0.538±0.154 L· kg^-1;AΜC_0～10:97.81±29.87 mg·h·L^-1,107.27±（39.54） mg·h·L^-1;AΜC_0～∞:153.32±65.64 mg·h·L^-1,174.01±71.03 mg·h·L^-1;CL :0.081±0.034 mg·h·L^-1,（0.074）±（0.033） L·kg^-1·h^-1;Cmax:20.51±5.12 mg·L^-1,20.60±5.05 mg·L^-1.There were no statistical significance between pharmacokinetic parameters of theophylline used alone and coadministered with gatifloxacin except T_1/2.CONCLUSION Fleroxacin and rufloxacin had minor influence on theophylline plasma and pharmacokinetic parameters of theophylline.Pefloxacin had marked influence on theophylline plasma and pharmacokinetic parameters of theophylline.gatifloxacin had minor influence on theophylline plasma and pharmacokinetic parameters of theophylline except T_1/2.更多还原