Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats

1. This study investigates the influence of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats.

2. The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10?mg/kg) with or without pretreatment with quercetin (20?mg/kg/day for 7 days) were investigated. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism.

3. The results showed that when the rats were pretreated with quercetin, the C_max (2.16?±?0.40 vs. 1.33?±?0.21?mg/L) and the AUC_(0–t) (13.89?±?1.22 vs. 7.34?±?0.75?mg·h/L) of losartan increased significantly (p?<?.05), and while the C_max (0.76?±?0.09 vs. 1.14?±?0.18?mg/L) of EXP3174 decreased significantly compared to the control (p?<?.05). The t_1/2 of losartan was prolonged from 3.27?±?0.45?h to 4.74?±?0.51?h (p?<?.05). The results also indicated that quercetin could increase losartan absorption rate by inhibiting the activity of P-gp and decrease its metabolic stability by inhibiting the activity of CYP450 enzyme.

4. These results indicated that the herb–drug interaction between quercetin and losartan might occur when they are co-administered in rats, quercetin could increase the systemic exposure of losartan and decrease the plasma concentration of EXP3174, possibly by inhibiting the activity of P-gp or CYP450 enzyme.