Influence of Polygonatum sibiricum Polysaccharide on the Plasma Pharmacokinetics of Valsartan in Rats and the Involvement of CYP3A1/2

Background Polygonatum sibiricum polysaccharide (PSP) combining with valsartan was focused on mimicking their combination for diabetes and hypertension to guide the clinical drug combination. Materials and Methods PSP (100, 200, and 400 mg/kg) was coadministered with valsartan was conducted in rats through a 10-day pretreatment. Single administration of valsartan (10 mg/kg) served as a control. The rat liver microsomes were employed for assessing the metabolic stability of valsartan and the activity of CYP3A1/2 through the probe-substrate assay. Results An in vivo pharmacokinetic study showed that PSP significantly increased the AUC, prolonging t 1/2 , and suppressed the clearance rate, which was enhanced by increasing PSP concentrations. In vitro , PSP significantly inhibited the intrinsic clearance rate of valsartan and improved its metabolic stability. Moreover, CYP3A1/2 was significantly inactivated by PSP, as revealed in rat liver microsomes, which was concentration-dependent. Conclusion Combination of PSP with valsartan prolonged the systemic exposure of valsartan, increasing the risk of hypotension and might influence the hypoglycemic effect of PSP. The inhibited CYP3A1/2 activity might mediate this interaction.