Pharmacokinetics And Drug Interactions Of Shaoyao-Gancao Decoction

Shaoyao-Gancao decoction（SGD）is a traditional Chinese medicinal formula,which is widely used to treat pains,inflammation and muscle cramps,etc.In this paper,the pharmacokinetic behaviors and drug interactions of SGD were studied by using LC-MS/MS technique.The effect of antibiotics on pharmacokinetics of SGD was studied.Pretreated with broad-spectrum antibiotics reduced the plasma exposure of paeoniflorin and liquiritin significantly in rats.The seven glycosides are comparatively stable in the rat duodenal contents,but were degraded rapidly and completely in the rat colonic contents.Antibiotics decreased the exposure of glycyrrhetinic acid and liquiritigenin by suppressing the colonic microbiota.The difference of pharmacokinetic behaviors of paeonia lactiflora,liquorice and SGD was studied.Although the contents of paeoniflorin and albiflorin in the extract of paeonia lactiflora and liquorice（SGE）are only 60%of that in the extract of Paeonia lactiflora（SYE）,there was no significant difference of their plasma exposure in rats between SGE and SYE.Compared with paeonia lactiflora and liquorice,the t_1/2 and MRT of albiflorin and liquiritin increased significantly.The compatibility of Paeonia lactiflora and licorice improved the absorption of the components in rats.The relationships of paeoniflorin,glycyrrhizic acid and glycyrrhetinic acid were studied.Paeoniflorin has a weak inhibitory effect on the transporter OATP 1B1.Glycyrrhizic acid is the substrate of transporter BCRP,OATP 1B1 and OATP 1B3,it also has inhibitory effects on both of the uptake transporters.Glycyrrhetinic acid has strong inhibitory effects on the transporter OATP 1B1 and OATP 1B3.When SGD is used together with antibiotics,the efficacy of SGD might be influenced by the drug-drug interactions（DDIs）.The DDIs between Paeonia lactiflora and liquorice might be able to promote their efficacy.When SGD is used together with drugs which are the substrates or inhibitors of transporters,attention should be paid to the probable DDIs induced by transporters.