关键词: 高原低氧, 药物动力学, 复方新诺明, 肺功能

Abstract: AIM: To explore the relationship between the pulmonary function changes and pharmacokinetics of the trimethoprim-sulphamethoxazole combination (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 adaptation 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 performance 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 function parameters of cotrimoxazole were calculated by DAS 2.0 and SPSS 13.0 statistical software in three groups after administration of SMZ Co tablets.RESULTS: There were statistically significant differences between the plain group and the rapid ascent group in the pharmacokinetics parameters of SMZ CO which include elimination rate constant (Ke), 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 Ke, MRT and t_1/2, and between rapid ascent group and adaptation group in the pharmacokinetics parameters which contain t_1/2 and apparent volume 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 ascent group(P<0.01) and the FEF50%, maximal midexpiratory flow (MMEF%), forced expiratory volume (FEV%), forced vital capacity (FVC%) and vital capacity (VC%) were decreased in the adaptation group (P<0.05 or 0.01).There were positive correlation between PEF%, FEF50% and AUC and negative correlation between FVC%, PEF%, FEF50%, MMEF%, FEV/FVC% and t_1/2, V/F.CONCLUSION: Pulmonary function changes have significant effect on AUC, t_1/2, V/F of SMZ CO pharmacokinetics in plateau environment.

Key words: high altitude hypoxia, pharmacokinetics, SMZ Co, pulmonary function