西替利嗪与左西替利嗪对大鼠氨茶碱血药浓度的影响

摘要

目的：探讨手性药物左西替利嗪与西替利嗪对氨茶碱代谢的影响。方法采用反相高效液相色谱法，色谱柱为 Hypersil BDS C18柱(250 mm ×4.6 mm，5μm)，流动相为水-甲醇（85：15），流速为1.0 mL / min，柱温为35℃，检测波长为275 nm。SD 大鼠，随机分为单用氨茶碱组（APL 组）、左西替利嗪+氨茶碱组（LCZ + APL 组）和西替利嗪+氨茶碱组（CZ + APL 组），每组8只（雌雄各半）。分别在给药0，2，4，6，8 h 时采血测定氨茶碱的血药浓度，分析药代动力学参数。结果与 LCZ + APL 组比较，APL 组氨茶碱的给药后初始血管浓度（ Co）、消除速率常数（Ke）、药物半衰期（ t1/2）、清除率（ CL）、药时曲线下面积（ AUC）、表观分布容积（ Vc）有显著性差异（ P ＜0.01或P ＜0.05）。与 CZ + APL 组比较，APL 组氨茶碱的 Ke，t1/2，CL，AUC 有显著性差异（ P ＜0.05），而 Co 及 Vc 无显著差异（ P ＞0.05）。与LCZ + APL 组比较，CZ + APL 组氨茶碱的 Ke，CL，Co，AUC 有显著性差异（ P ＜0.01或 P ＜0.05），t1/2无显著性差异（ P ＞0.05）。结论左西替利嗪与西替利嗪均可使氨茶碱的血药浓度升高、代谢率减慢，同时西替利嗪使氨茶碱血药浓度升高的作用比左西替利嗪更明显。%Objective To investigate the effects of chiral drug cetirizine and levocetirizine on the metabolism of aminophylline in rats. Methods The plasma concentration of aminophylline was detected by RP - HPLC with a BDS C18 column(250 mm × 4. 6 mm,5 μm). The mobile phase was water - methanol solution(85 : 15)at a flow rate of 1. 0 mL / min. The column temperature was 35 ℃. The detec-tion wavelength was 275 nm. The SD rats were randomly divided into the aminophylline group(APL group),levocetirizine plus amino-phylline group(LCZ + APL group)and cetirizine plus aminophylline group(CZ + APL group),8 rats in each group. The plasma concentra-tion of the aminophylline in rat was detected at the different timepoints of 0,2,4,6,8 h after administration and the pharmacokinetic parameters were analyzed. Results The initial plasma concentration( C0),elimination rate constant(Ke),half life( t1 / 2),clearance rate ( CL),area under curve( AUC)and apparent volume of distribution( Vc)of aminophylline had statistical differences between the APL group and the LCZ + APL group( P 0. 05). Ke,CL,C0 and AUC of aminophylline had statistical differences between the CZ + APL group and the LCZ + APL group,without including t1 / 2( P > 0. 05). Conclusion Levocetirizine and cetirizine both can elevate the plasma concentration and decrease the metabolic rate of amino-phylline. Furthermore,the effect of cetirizine for elevating blood aminophylline concentration is more significant than that of levocetirizine.