头孢曲松钠在胆汁中的浓度测定和药动学的实验研究

Determination of ceftriaxone sodium and its pharmacokinetics in rabbit bile

目的研究头孢曲松钠在胆汁中的浓度及其药动学,为预防和治疗胆系感染用药提供参考和依据。方法家兔行胆总管造瘘术,静脉注射头孢曲松钠后不同时间采集胆汁标本,采用高效液相色谱法测定胆汁中的药物浓度。用上海宏能药动学软件分析并得出药动学参数。结果家兔静脉注射头孢曲松钠后迅速分布,在胆汁中t_(max)为(0.036±0.094)h;ρ_(max)为(1509.20±584.60)mg·L^(-1);消除相t_(1/2)为(3.31±0.59)h。8 h胆汁中药物浓度为(43.86±12.65)mg·L^(-1),远超过胆道常见致病菌的MIC_(90)。结论头孢曲松钠有大量原形药物经胆道排泄,在胆汁中具有很高浓度,可作为预防和治疗胆道感染的优选药物。

OBJECTIVE To determine the concentrations of ceftriaxone sodium in rabbit bile and investigate its pharrnacokinetic parameters. METHODS The rabhits were administered intravenously with ceftfiaxone and the concentrations in bile were measured by HPLC. The pharmacokinetic parameters of ceftriaxone were analyzed by Shanghai Hongneng pharmacokinetic software. The maximum concentration（ρmax）, peak time（tmax）,half-life time（t1/2）,clearance（CL） and apparent volume of distribution（VD） were obtained. RESULTS After a single intravenous administration of 75 mg· kg ^- 1 ceftriaxone,ρmax （ 1 509.20 ± 584.60 ） mg·L^- 1 was reached at tmax （0.036 ± 0.094） h in bile and t 1/2 was （3.31 ± 0.59） h .The concentration of ceftriaxone at 8 h was（43.86 ± 12.65） mg· L^-1, which remained much higher than the reported 90% minimum inhibitory concentration （MIC90）of most biliary pathogens. CONCLUSION Ceftriaxone reaches high concentration in bile, which indicates that it is a practical and promising antibiotic for the treatment of biliary tract infection.