Effect of Wuziyanzong pill on metabolism of dapoxetine in vivo and in vitro
Abstract
&NA; In vitro incubation of rat liver microsomes with 30 &mgr;L of 100 &mgr;mol·L−1 dapoxetine and 30 &mgr;L of 10, 100, 250, 500, 1000, 2500, or 5000 &mgr;g·mL−1 Wuziyanzong pill was performed at 37 °C for 60 min. Dapoxetine concentration was analyzed by high performance liquid chromatography (HPLC). The half maximal inhibitory concentration (IC50) of Wuziyanzong pill on metabolism of dapoxetine was 296.10 &mgr;g mL−1 in vitro. Twelve SD rats were randomly divided into 2 groups: Control group and Wuziyanzong pill group. The two groups were administrated with 10 mL·kg‐1 saline (Control group) or 10 mL·kg‐1 Wuziyanzong pill solution (Experimental group, solution contained 200 mg mL‐1 Wuziyanzong pill) for 15 consecutive days. Following administration of saline or Wuziyanzong pill on the 15th day, 20 mg kg‐1 dapoxetine was administered to all rats. Blood was collected from the tail vein (0.3 mL) at multiple time points, and ultra‐high performance liquid chromatography tandem mass spectrometry (UHPLC‐MS/MS) was used to determine the concentration of dapoxetine and its main metabolites, dapoxetine‐N‐oxide and desmethyldapoxetine in rats. Pharmacokinetic analysis of dapoxetine showed that area under the concentration‐time curve (AUC) and mean maximum plasma concentration (Cmax) of the Wuziyanzong pill group were decreased, while plasma clearance (CLz) was increased compared with control group (P < 0.01). The HPLC method for determination of dapoxetine in vitro was accurate and…
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