醋柳愈酯的体内代谢及药代动力

THE PHYSIOLOGIC DISPOSITION AND PHARMACOKINETICS OF GUAIACOLACETYLSALICYLATE IN RATS

本文用薄层扫描定量法研究了醋柳愈酯在大鼠体内的代射,并测定代谢物水杨酸(SLA)的血药浓度,所得药一时数据依一定程序进行曲线拟合,计算药代动力学参数。并直接观察在大鼠体内的组织分布和在尿、粪、胆汁中的排泄。以肌肉、肺最高,脾、血浆次之,肾、睾丸、心、肝、脑、脂肪均有分布。小部分SLA径肾排泄,粪及胆汁排出量极低。

Guaiacol acetylsalicylate (GASL) has been shown to possess significant anti-inflammatory, antipyretic and expectorant activities and has been used clinically in chronic bronchitis with fairly good results. In the present work, the absorption, distribu-tion and excretion of metabolites of the drug were studied in rats using quantitative TLC scanning technique. GASL was shown to be unstable, in rat gastrointestinal tract and guaiacol salicylate (GSLT) and salicylic acid (SLA) were found in plasma.The plasma SLA concentration-time curve obtained after oral administration of GASL to rats was shown to fit a one compartment open model with the following pharmacokinetic parameters:T_(1/2)ka=1.25h, T_(1/2)ke=3.28h, ka=0.5554/h, ke=0.2111/h,T_(max)=3.02h, C_(max)=331.46μg/ml, AUC=2832.93μg/ml·hThe SLA concentration was found to be high in muscle, moderate in spleen, testicle, kidney, lung, plasma, heart and liver and low in brain. The GSLT concentration was found to be low in plasma and organs.Within 24 h following ig administration of GASL the total SLA excreted in urine and feces was 10.9 and 0.41 of the GASE dose, respectively.