【摘要】 目的:研究尿液pH值对大鼠体内苯丙醇胺、伪麻黄碱和芬氟拉明药动学的影响。方法:大鼠随机分成3组,分别灌胃生理盐水、氯化铵和碳酸氢钠以使大鼠尿液pH呈正常、偏酸性或偏碱性状态;3组大鼠灌胃苯丙醇胺、伪麻黄碱和芬氟拉明后,用柱前衍生-HPLC法分别测定血浆中3种药物的浓度,估算相应的药动学参数并比较。结果:当尿液pH值降低时,苯丙醇胺、伪麻黄碱和芬氟拉明的吸收相血药浓度、Ka、cmax、tmax和Vd基本不变,但消除相血药浓度、t1/2、MRT、AUC0-∞显著减小,且CL/F明显增加。结论:苯丙醇胺、伪麻黄碱和芬氟拉明的吸收不受尿液酸碱度变化的影响,但随着尿液pH值的减小,其消除显著加快。更多还原

【Abstract】 Aim:To investigate the influence of urinary pH modification on the pharmacokinetics of phenylpropanolamine,pseudoephdrine and fenfluramine in rats. Methods: Rats were divided into three groups, and urine pH of each group was modified by repeated oral dosing of physiological saline, ammonium chloride and sodium bicarbonate, to physiological, meta-acidic and meta-alkaline levels, respectively. At the same time, phenylpropanolamine, pseudoephdrine and fenfluramine were orally given to the three groups. The plasma concentrations of the three drugs were determined by HPLC after precolumn derivatization, and the pharmacokinetic parameters were estimated and compared. Results: Decrease in urinary pH caused no changes to plasma concentrations in the absorption phase, Ka, cmax, tmax and Vd of the three species, but their plasma levels in the elimination phase, t1/2s, MRTs and AUCs reduced significantly, while CL/Fs significantly increased. Conclusion: The absorption of phenylpropanolamine, pseudoephdrine and fenfluramine was not affected by the urinary pH modification, but decrease in urinary pH resulted in their enhanced elimination.更多还原