左旋奥硝唑在人体内的构型转化及药动学研究

目的: 研究左旋奥硝唑在健康人体内的构型转化及单次口服左旋奥硝唑的人体药代动力学。 方法: 24名健康志愿者,单剂量口服左旋奥硝唑片500 mg后72 h采集血浆样品,用手性拆分色谱柱分离、检测血浆中左旋奥硝唑与右旋奥硝唑;以高效液相色谱法测定血药浓度,用DAS ver 2.0软件计算药动学参数。 结果: 在给药后的健康志愿者体内未检出右旋奥硝唑。左旋奥硝唑人体内主要药动学参数分别为:C_max=(28.86 ± 8.77) mg·L^-1,AUC_0→t=(453.9±184.4)mg·h·L^-1,T_max=(0.57±0.36) h,V₁/F=(31.7±15.4)L,CL/F=(2.42±0.69)L·h^-1,t_1/2β=(14.7±2.1)h,MRT=(17.6±1.8)h。 结论: 健康志愿者口服左旋奥硝唑后,在体内未发生构型转化。因而在对左旋奥硝唑血浆样品进行检测时,可以不必考虑消旋化带来的影响。

Objective: To study the chiral inversion and pharmacokinetics of laevo-ornidazole in human. Methods: 24 Chinese volunteers were administrated with an oral dose of 500 mg laevo-ornidazole.Then 3 mL blood was sampled after 72 h to detect the plasma concentrations of laevo-ornidazole and dextro-ornidazole on a chiral HPLC column.The pharmacokinetic parameters were measured by DAS ver 2.0 software. Results: Dextro-ornidazole was not found in all 24 plasma samples from different volunteers.The pharmacokinetic parameters of laevo-ornidazole were as following:C_max=(28.86±8.77)mg·L^-1,AUC_0-t=(453.9±184.4)mg·h·L^-1,T_max=(0.57±0.36)h,V₁/F=(31.7±15.4)L,CL/F=(2.42±0.69)L·h^-1,t_1/2β=(14.7±2.1)h,MRT=(17.6±1.8)h. Conclusion: The chiral inversion from laevo-ornidazole to dextro-ornidazole does not occur.So we can investigate the pharmacokinetics of laevo-ornidazole without consideration of its racemization.