Effects of quinolones on pharmacokinetics of theophylline

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)·h~(1);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),P0.01;T_(1/2):4.95±1.67 h,6.69±2.01 h,P0.01;V:(0.584)±0.149 L·kg~(-1),0.511±0.126 L· kg~(-1),P0.05;AΜC_(0～10):97.71±40.09 mg·h·L~(-1),126.11±42.72 mg·h·L~(-1),P0.01;AΜC_(0～∞):136.05±83.40 mg·h·L~(-1),202.10±99.81 mg·h·L~(-1),P0.01;CL:0.091±0.038 L·kg~(-1)·h~(-1),(0.056)±0.018 L·kg~(-1)·h~(-1),P0.01;Cmax:18.94±4.89 mg·L~(-1),21.82±5.40 mg·L~(-1),P0.05.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).