Effect of Shaofu Zhuyu Decoction on in vivo pharmacokinetics and metabolites of Ibuprofen in rats

Objective To explore the effect of Shaofu Zhuyu Decoction(SZD) on in vivo pharmacokinetic characteristics and metabolites of Ibuprofen in rats.Methods HPLC-DAD method was established to quantitatively analyze the pharmacokinetic parameters of Ibuprofen combined with SZD.UHPLC-QTOF-MS,MSE,and mass defect filtering(MDF) were used to investigate the metabolite changes of Ibuprofen in plasma,feces,and urine in rats after ig administration of Ibuprofen combined with SZD.Results The in vivo absorption of single Ibuprofen in rats was quick,which could reach the peak in 0.5 h.After combined with SZD at different concentration,tmaxwas prolonging(P 0.01) and Cmaxwas decreasing but no statistic significance was found compared with the Ibuprofen group.When Ibuprofen was used with SZD at the clinical equivalent amount,AUC values were significantly increased(P 0.05),which showed that bioavailability was increased and the apparent clearance was decreased.When Ibuprofen was used with SZD at five-fold clinical equivalent amount,the t1/2zof Ibuprofen was decreased significantly(P 0.05).The decreases of blood-drug concentration after the administration for 2 h in Ibuprofen or Ibuprofen with SZD groups were slower than those in SZD single group.These indicated that the pharmacokinetic characteristics of Ibuprofen were different from those in Ibuprofen with SZD groups,which were dependent on the dosages of SZD.The metabolites of Ibuprofen used signally were 2′-hydroxy-Ibuprofen,2′hydroxy-Ibuprofen-glucuronide,2′-carboxy-Ibuprofen,and Ibuprofen-glucuronide.Total 17 metabolites of Ibuprofen were identified from plasma,urine,and feces after combined with SZD.Hydroxylation,degradation,acetylation,and hydroxy-sulfate products were identified in rat feces,methylation,hydroxylation,acetylation,and sulfation products were identified in rat plasma.There was no significant difference of metabolites in urine except cysteine covalent conjugation.Conclusion The results provide the basis for the clinical use of Ibuprofen combined with SZD to illustrate the pharmacodynamic changes and mechanism.