高原环境肺功能改变对复方新诺明药物动力学的影响

目的：探讨高原低氧条件下肺功能与复方新诺明（sulfamethoxazole Co，SMZ Co）药物动力学的关系。方法：采用高效液相色谱法测定平原、急进高原和久居高原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。应用德国Jegger肺功能仪测定3组肺功能。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物动力学和肺功能参数。结果：急进高原组受试者的药动物力学参数消除速率常数（Ke）、AUC、平均驻留时间（MRT）、半衰期（t1/2）、清除率（CL）与平原组比较差异有统计学意义，久居高原组受试者的药物动力学参数Ke、MRT、t1/2与平原组比较差异有统计学意义，急进高原纽受试者的药动物力学参数t1/2、表观分布容积（V／F）与久居高原组比较差异有统计学意义。急进高原组的呼出25％肺活量时最大呼气峰流速（FEF25％）和最大呼气峰流速（PEF％）值大于平原和久居组（P〈0．01），久居组呼出50％肺活量时最大呼气峰流速（FEF50％）、最大呼气中段流速（MMEF％）、用力呼气容积（FEV％），用力肺活量（FVC％）和肺活量（VC％）与急进高原和平原组相比显著下降（P分别〈0．05和0．01）。最大呼气峰流速（PEF％）、FEF50％与AUC正相关；FVC％、PEF％、FEF50％、MMEF％和用力呼气容积占用力肺活量的百分比（FEV／FVC％）与t1/2和VIF负相关。结论：高原环境肺功能改变对复方新诺明药物动力学参数AUC、t1/2，和V/F有显著影响。

Effects of pulmonary function changes on pharmacokinetics of the trimethoprim-sulphamethoxazole combination in plateau environment

To explore the relationship be-tween the pulmonary function changes and pharmacoki-netics of the trimethoprim-sulphamethoxazole combina-tion (SMZ CO) under hypoxic condition of the Qinghai-Tibet plateau. METHODS: The Han Chinese healthy young male volunteers were divided into three groups which involve plain group, rapid ascent group and ada-ptation group. All subjects in this study were treated with a single dose of SMZ Co tablets, the concentration of SMZ Co in plasma was determined by high perfor-mance liquid chromatography (HPLC) at 15 different time points and the pulmonary function parameters were determined by Jegger pulmonary function instrument of Germany. The pharmacokinetics and pulmonary func-tion parameters of cotrimoxazole were calculated by DAS 2.0 and SPSS 13.0 statistical software in three groups after administration of SMZ Co tablets. RE-SULTS: There were statistically significant differences between the plain group and the rapid ascent group in the pharmacokinetics parameters of SMZ CO which in-clude elimination rate constant ( K_e) , area undercurve ( AUC ) , mean residence time ( MRT ) , half-life (t_(1/2)) , clearance rate (CL), the plain group and the adaptation group in the pharmacokinetics parameters which involve K_e, MRT and t_(1/2), and between rapid ascent group and adaptation group in the pharmacoki-netics parameters which contain t_(1/2) and apparent vol-ume of distribution ( V/F) . Compared with other two groups, the forced expiratory flow after 25% of vital capacity expelled (FEF25 %) and peak expiratory flow (PEF%) were significantly raised up in the rapid as-cent group( P < 0.01)and the FEF50% , maximal mi-dexpiratory flow (MMEF% ), forced expiratory volume (FEV%), forced vital capacity (FVC%) and vital ca-pacity (VC % ) were decreased in the adaptation group (P < 0.05 or 0.01). There were positive correlation between PEF% , FEF50% and AUC and negative cor-relation between FVC%, PEF%, FEF50%, MMEF%, FEV/FVC% and t_(1/2), V/F. CONCLU-SION: Pulmonary function changes have significant ef-fect on AUC, t_(1/2) , VIF of SMZ CO pharmacokinetics in plateau environment.