氧氟沙星在肝纤维化大鼠体内的药动学及生物利用度  

Pharmacokinetics and Bioavailability of Ofloxacin in Hepatic Fibrosis Rats

作　　者：陈曼[1] 汪晖[1] 易有荣[2] 

机构地区：[1]武汉大学医学院药理学系,武汉430071 [2]武汉大学医学生物结构中心,武汉430071

出　　处：《中国药学杂志》2006年第8期623-626,共4页Chinese Pharmaceutical Journal

摘　　要：目的研究肝纤维化状态下氧氟沙星的药动学及绝对生物利用度的改变,为临床肝纤维化病人合理用药提供实验依据。方法建立大鼠复合因素肝纤维化模型,荧光分光光度法检测氧氟沙星iv及po后的血药浓度,计算药动学参数和生物利用度。结果氧氟沙星iv时药物浓度-时间曲线符合二室模型,与正常对照组相比,肝纤维化组分布半衰期(t1/2α)延长137.8%,分布速率常数(k12)减少68.7%,k21减少53.6%,清除率(CL)降低12.5%;po时药物浓度-时间曲线符合一室模型,与正常对照组相比,肝纤维化组曲线下面积(AUC)减少14.7%,吸收半衰期[t1/2(K01)]延长50.4%,消除半衰期[t1/2(K10)]延长41.5%,达峰时间(tmax)延长38.2%,峰浓度(ρmax)降低41.3%。研究进一步发现,肝纤维化组绝对生物利用度较正常对照组减少了24.1%。结论肝纤维化时氧氟沙星的吸收、分布及排泄均减慢,生物利用度减少,峰浓度降低。OBJECTIVE To investigate the changes of pharmacokinetics and bioavailability of ofloxacin for its reasonable use in the patients with hepatic fibrosis. METHODS Animal model with hepatic fibrosis was prepared. 0floxacin plasma concentrations in rats were determined after intravenous injection and oral administration. Pharmacokinetic parameters and absolute bioavailability were calculated. RESULTS The concentration-time curve of ofloxacin was fitted to a two-compartment model after intravenous injection. Hepatic fibrosis resulted in a 137.8% increase in the half life, and resulted in 68.7%, 53.6% and 12.5% decrease in the rate constants （ k12 and k21） and clearance（CL） ,respectively, as compared with control group. Meanwhile, the concentration-time, curve was fitted to an one-comparement open model after oral administration. Hepatic fibrosis resulted in 50.4%, 41.5 % and 38.2% increase in the half life of absorption [ t1/2（k01）], half life of elimination [ t1/2（k10）] and peak time, respectivley;resulted in 14.7% and 41.3% decrease in the area under the curve （AUC） and peak concentration （ρmax） is respectively, as compared with control group. The absolute bioavailability of ofloxacin in hepatic fibrosis rats decreased 24.1% compared with control group. CONCLUSION The absorption, distribution and elimination of ofloxacin are slower, the absolute bioavailability and ρmax, are reduced in the status of hepatic fibrosis.

关 键 词：肝纤维化 药动学 绝对生物利用度 

分 类 号：R969[医药卫生—药理学]