中文摘要：

探讨磺胺甲噁唑（SMZ）在平原汉族、高原世居汉族和藏族健康男性志愿者体内的药物代谢动力学特征。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（N4-acetyl-SMZ）的血药浓度,DAS 2.0软件计算药物动力学参数。与平原志愿者比较,磺胺甲噁唑在高原世居汉族和藏族健康男性志愿者体内的药物代谢动力学发生显著变化,主要表现为半衰期延长、清除率降低。高原世居藏族的AUC0-∞显著小于高原世居汉族,其他药物代谢动力学参数无显著性差异。实验结果表明,在高原低氧环境中,磺胺甲噁唑的药物动力学特征发生显著改变。研究结果为高原世居汉族和藏族临床合理应用磺胺甲噁唑提供参考依据。

英文摘要：

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain（PH） and native Han and Tibetan healthy volunteers living at high altitude（HNH and HNT）.After healthy volunteers were administrated orally cotrimoxazole tablets,plasma concentration of sulfamethoxazole and metabolite N 4-acetylsulfamethoxazole was determined by RP-HPLC,and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters.The main pharmacokinetic parameters t 1/2 of sulfamethoxazole in PH,HNH and HNT were,respectively,9.30 ± 1.11,10.99 ± 1.23 and 10.44 ± 1.05 h;t max were 1.4 ± 0.3,2.0 ± 1.1 and 1.8 ± 0.4 h;C max were 94.42 ± 15.26,89.33 ± 7.67 and 87.43 ± 11.61 μg·mL 1;AUC 0 t were 1 202.5 ± 238.3,1 434.7 ± 193.9 and 1 302.8 ± 103.0 μg·h·mL 1;AUC 0 ∞ were 1 240.7 ± 255.3,1 511.5 ± 211.9 and 1 363.9 ± 116.5 μg·h·mL 1;CL were 1.01 ± 0.22,0.81 ± 0.12 and 0.89 ± 0.08 L·h 1 ·kg 1;V were 13.27 ± 1.73,12.81 ± 2.15 and 13.28 ± 1.20 L·kg 1.Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH.The t 1/2 was significantly higher and the CL was significantly lower in HNH and HNT than that in PH,and the AUC 0 ∞ was significantly lower in HNT compared with HNH.This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia.This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.