title: [Effect of piperine on metablism and distribution of nortriptyline in mice].
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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Pharmaceutical Research Institute, Second Xiangya Hospital, Central South University, Changsha 410011; Department of Pharmacy, Jiangxi Provincial People' Hospital, Nanchang 330006, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Cai
authors.forename: Jiawen
authors.initials: J
authors.lastname: Liu
authors.forename: Lanlin
authors.initials: L
authors.lastname: Li
authors.forename: Shaolin
authors.initials: S
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Wenxing
authors.initials: W
authors.lastname: Peng
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D052117:Benzodioxoles / Q000737:chemistry*; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051379:Mice; D009661:Nortriptyline / Q000493:pharmacokinetics*; D010880:Piperidines / Q000737:chemistry*; D053284:Polyunsaturated Alkamides / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D014700:Verapamil
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D009661:Nortriptyline; D014700:Verapamil; C008922:piperine