【摘要】 目的探讨磺胺甲噁唑及其代谢产物N4-乙酰磺胺甲噁唑在健康男性志愿者体内的药物动力学。方法20名受试者口服复方新诺明片后,采用RP-HPLC法测定磺胺甲噁唑及其代谢产物N4-乙酰磺胺甲噁唑的血药浓度,DAS2.0软件计算药物动力学参数。结果磺胺甲噁唑及其代谢产物N4-乙酰磺胺甲噁唑的主要药物代谢动力学参数t1/2分别为9.30±1.11、12.43±2.43h,AUC0-t为1202.5±238.3、240.9±47.1μg·h·mL-1,CL为1.01±0.22、1.99±0.43L·h-1·kg-1,Vd为13.27±1.73、34.49±4.38L·kg-1,MRT为12.06±0.94、15.40±1.81h。结论磺胺甲噁唑在体内吸收迅速、消除半衰期较长,其乙酰化代谢途径为生成限速代谢模式,20名受试者中没有发现明显的快慢代谢分型。更多还原

【Abstract】 OBJECTIVE To study the pharmacokinetics of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole in healthy Chinese volunteers.METHODS 20 healthy Chinese volunteers were administrated orally of cotrimoxazole tablets.Then the plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole were determined by RP-HPLC,and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters.RESULTS The main pharmacokinetic parameters t1/2 of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole were 9.30 ± 1.11 h and 12.43 ± 2.43 h,respectively; AUC0 -t were 1202.5 ± 238.3 μg·h·mL -1 and 240.9 ± 47.1 μg·h·mL -1,CL were 1.01 ± 0.22 L·h -1·kg -1 and 1.99 ± 0.43 L·h -1·kg -1,Vd were 13.27 ± 1.73 L·kg -1 and 34.49 ± 4.38 L·kg -1,MRT were 12.06 ± 0.94 h and 15.40 ± 1.81 h.CONCLUSION Sulfamethoxazole has rapid absorption and long half-life time of elimination after oral administration,and the elimination of N4-acetylsulfamethoxazole was a formation rate-limited metabolism.Slow and fast acetylators for sulfamethoxazole were not be found in this study.更多还原