ABSTRACT
Objective: 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. Methods: 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 atfer giving the above drugs, each mice was intraperitoneally injected nortriptyline (13 mg/kg). The mice were sacriifced by picking off eyeballs at the time intervals of 5, 15, 30 min, and 1, 2, 4, 6, 8 and 12 h, andthe 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. Results: hTe 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 signiifcantly different from those of untreated mice. Conclusion: 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 blood-brain barrier.
ABSTRACT
This study is to screen 23 blank O/W type microemulsion (ME) samples, that is 15 samples from our laboratory, and 8 samples from literature; compare the conductivity-water content curve (CWCC) method and visual method in determining the critical water content during O/W type MEs' formation, to analyze the deficiency and the feasibility of visual method and to exploxe scientific meanings of CWCC method in judging the critical water content of O/W type MEs during formation. The results show that there is a significant difference between the theoretical feasible CWCC method and visual method in determining the critical water content (P<0.001), and the results judged by conductivity is higher than that by eye-based water content. Therefore, this article firmly confirmed the shortcomings of visual method and suggested that the eye-base "critical water content" may falls into continuous ME stage during O/W MEs' formation. Further more, the CWCC method has theoretical feasibility and scientific meanings in determining the critical water content of O/W type MEs during formation.