[Effect of piperine on metablism and distribution of nortriptyline in mice]

To study the pharmacokinetics and brain/plasma concentration ratio of nortriptyline at multiple doses in mice which were pre-treated with physiological saline, piperine and verapamil.

A total of 216 male Kun Ming mice [(25±3) g] were equally divided into 4 groups randomly. Each group was intragastrically administered physiological saline (B), piperine (170 μg/ kg), piperine (5 mg/kg) and verapamil (5 mg/kg) for 8 days. On the 8th day, 1 h after giving the above drugs, each mice was intraperitoneally injected nortriptyline (13 mg/kg). The mice were sacrificed by picking off eyeballs at the time intervals of 5, 15, 30 min, and 1, 2, 4, 6, 8 and 12 h, and the cerebra were collected and weighted. Nortriptyline in mouse plasma and brain was determined by HPLC-MS/MS. The pharmacokinetic properties of the plasma, brain and brain/plasma were calculated.

The AUC0-12 h of brain/plasma concentration ratio in the 170 μg/kg piperine group was significantly lower than that in the other groups (P<0.05), while the AUC0-12 h of brain/plasma concentration ratios in the 5 mg/kg piperine group and the verapamil group were not significantly different from those of untreated mice.

Piperine (170 μg/kg) may induce P-glycoprotein expression in the blood-brain barrier, while piperines at 5 mg/kg has no influence on P-glycoprotein expression in the bloodbrain barrier.