抗菌剂合用对芍药甘草汤中甘草酸生物利用度的降低作用及减少该作用的方法Ⅱ:合用西药对于芍药甘草汤中甘草酸生物利用度的影响(英文)

Reduction of bioavailability of glycyrrhizin from Shaoyao-Gancao-Tang by co-administered synthetic drugs and ways of minimizing it(PartⅡ) Effects of co-administered synthetic drugs on the bioavailability of glycyrrhizin from Shaoyao-Gancao-Tang S

在第I部分中 ,已经报告了芍药甘草汤 (SGT)的连续给药提高了SGT中甘草酸 (glycyrrhizin,GL)的生物利用度。在本文 ,即本研究的第II部分 ,对在溃疡治疗中常和SGT合用的西药 ,如组织胺H2 受体拮抗剂cimetidine,抗胆碱药scopolaminebutylbromide(SBB) ,由一个质子泵抑制剂 (omeprazole,OPZ)和两种抗菌剂(amoxicillin,AMPC,andmetronidazole,MET)所组成的三剂疗法OAM等 ,对于SGT中GL生物利用度的影响进行了考察。实验结果显示 ,cimetidine或SBB的合用对SGT中GL的生物利用度没有显著影响 ,但OAM的合用却有显著的降低作用。OAM降低作用的要因药物经实验证明为抗菌剂组合AMPC_MET ,而非质子泵抑制剂OPZ。AMPC_MET作用的原因机制在于其显著地降低了肠内细菌的将GL代谢成甘草次酸 (18β_glycyrrheticacid,GA)的活性。该结果表明 ,含有AMPC_MET的三剂疗法如OAM等不适合和SGT同时给药。

In part I,we reported that the repetitive administration of Shaoyao-Gancao-Tang(SGT)increased the bioavailability of glycyrrhizin(GL)in SGT.In clinic,SGT is sometimes used together with some synthetic drugs.In this partⅡ,the influences of co-administered synthetic drugs on the pharmacokinetic fate of GL from SGT were investigated.The results showed that the co-administration of either a histamine2-receptor antagonist(cimetidine)or an anticholinergic drug(scopolamine butyl bromide,SBB)did not clearly influence the bioavailˉability of GL in SGT.However,the co-administration of a triple therapy OAM consisting of a proton pump inˉhibitor(omeprazole,OPZ)and two antibacterial drugs(amoxicillin,AMPC,and metronidazole,MET)markedly reduced the plasma GA concentration.The reduction of plasma GA by OAM was shown to be due to the anˉtibacterial drugs AMPC-MET,not the proton pump inhibitor OPZ.The mechanism of the reduction by AMˉPC-MET involved the severe decrease of the GL-metabolizing activity of intestinal bacteria by AMPC-MET.These results suggest that it is not appropriate to simultaneously administer AMPC-MET with SGT.