左氧氟沙星4种晶型的大鼠体内药动学研究

Study on Pharmacokinetics of Levofloxacin Polymorphs in Rats

目的研究左氧氟沙星4种晶型在SD大鼠体内药动学差异,评价其优势药用晶型,探讨药物晶型物质状态对临床用药的影响。方法 SD大鼠灌胃给予不同晶型左氧氟沙星固体原料药,高效液相色谱法测定血左氧氟沙星浓度,非房室模型计算大鼠体内药动学参数并在不同晶型之间进行比对。结果大鼠灌胃给予左氧氟沙星晶Ⅰ、Ⅱ、Ⅲ、Ⅳ型后,血液中峰浓度(Cmax)分别为6.984,9.692,9.405,6.424 mg·L-1;达峰时间(tmax)分别为0.6,0.9,1.0,1.0 h;半衰期(t1/2)分别为4.207,2.970,4.857,1.695 h;药-时曲线下面积(AUC(0→12 h))分别为31.478,42.385,32.406,31.636mg·h·L-1。结论大鼠口服不同晶型左氧氟沙星后,利用专业软件DAS 3.0对测得的血药浓度数据进行药动学参数计算,左氧氟沙星4种晶型未发现差异有统计学意义,但检测结果表明晶Ⅱ型血药浓度最高,血药浓度维持时间长,可能作为优势药用晶型用于产品生产。

Objective To study the pharmacokinetics difference of levofloxacin polymorphs in rats,evaluate the advantageous medical polymorph,and explore the effects of different polymorphs on clinical medicine. Methods Four crystal forms of levofloxacin were administered intragastrically to rats,and high performance liquid chromatography（ HPLC） was used to measure the contents of levofloxacin in rat plasma. The pharmacokinetic parameters were calculated and compared Results After a single oral dose,the peak plasma concentration（ Cmax） of crystal forms ofⅠ,Ⅱ,Ⅲ and Ⅳ of levofloxacin was 6. 984,9. 692,9.405,6. 424 mg·L^-1; the time to peak（ tmax） was 0. 6,0. 9,1. 0,1. 0 h; the half-life（ t1 /2） was 4. 207,2. 97,4. 857,1. 695 h;the area under the curve（ AUC0→12 h） was 31. 478,42. 385,32. 406,31. 636 mg · h · L^-1. Conclusion There is no statistically significant difference in pharmacokinetic parameters. However,compared with other crystal forms,plasma concentration of crystal form II is higher and maintained longer. Therefore,crystal form II of levofloxacin is an advantageous polymorph for medicine.