急进高原前后Wistar大鼠体内地塞米松药动学参数比较

目的: 建立血浆中地塞米松的含量测定方法,并用此法探讨平原组与急进高原组Wistar大鼠体内地塞米松的药动学特征。方法: 色谱柱固定相为Phenomene Gemini C₁₈ (4.6 mm×250 mm,5 μm),流动相为甲醇-水(80:20),流速为1.0 ml·min^-1,紫外检测波长为240 nm,柱温为25 ℃,内标为甲睾酮;7只Wistar大鼠于平原采血(平原组,P)后,相隔一周清洗期后急进高原(急进高原组,H),禁食12h后将0.056 g醋酸地塞米松片剂灌胃。于给药前(0 h,空白血浆)及给药后0.67,1,1.5,2,3,4,6,8,12及24 h由眼眶后静脉丛取血,采用高效液相色谱法测定Wistar大鼠单剂量灌胃后地塞米松血药浓度。结果: 血浆地塞米松浓度测定的线性范围为80~1 600 ng·ml^-1,r=0.999 2,最低检测限为80 ng·ml^-1。比较急进高原组与平原组大鼠体内地塞米松药动学参数,发现其发生了显著变化,药时曲线下面积从(616.848±68.585)μg·L^-1·h增大到(1 222.825±83.192)μg·L^-1·h,峰浓度增大、半衰期缩短、体内平均驻留时间延长、总清除率降低,且差异均有统计学意义,P<0.05。结论: 急进高原后,地塞米松在Wistar大鼠体内代谢过程发生明显变化,研究结果为平原和急进高原后临床合理应用地塞米松提供参考依据。

Comparative research on pharmacokinetic parameters of dexamethasone in Wistar rats before and after radical plateau

OBJECTIVE To establish a HPLC method for determination of dexamethasone in plasma and to investigate pharmacokinetics of dexamethasone in wistar rats lived in plain and highland after acute movement. METHODS HPLC conditions included: the column Phenomenex Gemini C₁₈ (4.6 mm×250 mm, 5 μm)as the stationary phase, methanol-water(80:20) as the mobile phase, a flow rate of 1.0 ml·min^-1, detection wavelength at 240 nm, and column temperature at 25 ℃. Methyltestosterone served as internal standard. One week wash-out period later, 7 wistar rats in plain group (P) and plateau group (H) underwent intragastric administration with 0.056 g of acetate dexamethasone tablets after fasting for 12h. Drug levels in blood from veins of eye socket were detected with high performance liquid chromatography before medication (0 h), and 0.67, 1, 1.5, 2, 3, 4, 6,8, 12 and 24 h after medication. RESULTS The linear range of dexamethasone was 80-1600 ng·ml^-1, r=0.999 2,the lower limit of detection was 80 ng·ml^-1. Dexamethasone pharmacokinetics parameters in group H were significantly different from those in group P, area under curve increased from (616.848±68.585)μg·L^-1·h to (1222.825±83.192)μg·L^-1·h, the Cmax in group H was significantly higher and intracorporal average residence time in group C were significantly prolonged, while half life and total body clearance in group H were reduced, with statistically significant differences (P<0.05). CONCLUSION Internal metabolic processes of dexamethasone in rats may significantly change after acute movement to highland, which may provide references for clinical rational application of dexamethasone in plains and in highland after acute movement.