中文摘要：

目的高原低氧环境血气变化对复方磺胺甲噁唑（复方新诺明）药动学影响。方法采用高效液相色谱法测定平原、急进高原和世居高原3组2个群体健康汉族男性青年志愿者口服单剂量复方新诺明前后15个时间点血浆药物浓度。应用美国NOVA血气分析仪测定平原、急进和久居高原组于实验当日晨7：30（服药前）动脉血血气。采用DAS2．0和SPSS13．0统计软件计算3组受试者口服复方新诺明片后磺胺甲噁唑的药动学和血气参数。结果急进高原组受试者的药动学参数艇，AUC，MRT，t1/2，CL与平原组有显著性差异，久居高原组受试者的药动学参数Ke，MRT，t1/2与平原组有显著性差异，急进高原组受试者的药动学参数t1/2，V与久居高原组有显著性差异。久居高原组和急进高原组血气的特征为低氧血症、呼吸性碱中毒和代谢性酸中毒。PaCO2，PaO2，SaO2，HCO3^-，CO2和BEecf与Ke正相关（P分别〈0.01和0．05）；与AUC，MRT和t1／2负相关（P分别〈0．01和0．05）。pH与MRT，t1／2正相关（P〈0．05）；与Ke负相关（P〈0．01）。O2Ct和O2CaP正相关。结论高原环境血气改变对复方新诺明药动学有显著影响。

英文摘要：

OBJECTIVE To investigate the effects of blood gas changes on the pharmacokinetics of compound sulfamethoxazole （SMZ Co） at the high altitude. METHODS The healthy male volunteers were divided into three groups： the control group, the short-term exposure group and the long-term exposure group. The subjects in these three groups were natives in the plain area, the plain natives who quickly entered into the high altitude area from the plain area and the inhabitants lived in the high altitude area for long time, respectively. All subjects in this study were treated with a single dose of SMZ Co tablet. Their plasma concentrations of SMZ Co were determined by HPLC before and at the different time points after treatment with CoSMZ, and the blood gas analyze was performed before taking the drug in each subject. The data were analyzed by DAS2.0 and SPSS 13.0 software. RESULTS There were significant differences in pharmacokinetic parameters of Ke, AUC, MRT, t1/2 and CL between the short-term exposure group and the control group, in Ke, MRT and t1/2 between the long-term exposure group and the control group, and in t1/2 and V between the long-term exposure group and the short-term exposure group. The blood gas analyze revealed the characteristics of hypoxemia, respiratory alkalosis and metabolic acidosis in the subjects of the short-term expesure group and the long-term exposure group. Each parameter of PaCO2, PaO2, SaO2, HCO3-, CO2, BEecf was correlated positively with the Ke of SMZ （P〈0.01 or 0.05）, however, was correlated negatively with AUC, MRT or t1/2 （P〈0.01 or 0.05）. pH was correlated positively with MRT and t1/2 （both P〈0.05）, but was correlated negatively with Ke （P〈0.01）. And there was the positive correlation between Vz/F and OeCt or O2Cap. CONCLUSION Blood gas changes significantly effect the pharmacokinetics of SMZ Co in the healthy mole volunteers at high altitude.