title: [Application of Cocktail Probe Drugs for Detecting Influences of Raw and Processed Phellodendri Cortex on Cytochrome P450 Isoforms].
abstract: OBJECTIVE
  To research and compare the influences of raw and processed Phellodendri Cortex on the cytochrome P450 four isoforms by Cocktail probe drugs, and to explore the processing principle of Phellodendri Cortex.
  
  
  METHODS
  SD rats were randomly divided into raw group,processed with rice-wine group, processed with salt-water group and blank control group, which were given raw decoction, processed with rice-wine decoction, processed with salt-water decoction (3.24 g/kg) and normal saline respectively for one week, then given the mixture of four probe drugs on the 8th day, and soon after the blood samples were obtained through the orbits at a series of time-points. HPLC method was used to determine the concentrations of probe drugs in rat plasma, and pharmacokinetic parameters were estimated by DAS3.0. The effect of raw and processed Phellodendri Cortex on cytochrome P450 were judged indirectly by the pharmacokinetic parameters.
  
  
  RESULTS
  Compared with the blank control group, the t½ significantly increased of theophylline in raw and processed with salt-water group. The CL/F significantly decreased and AUC(0-t) AUC(0-∞). significantly increased of theophylline in raw and processed with rice-wine groups. The t(½) AUC(0-∞) and AUC(0-∞) significantly decreased and CL/F significantly increased of dapsone in raw, processed with rice-wine and processed with salt-water group. The AUC(0-t) significantly increased of chlorzoxazone in raw and processed with salt-water group. The t(½), AUC(0-∞). and AUC(0-t) significantly decreased and CL/F significantly increased of chlorzoxazone in processed with rice-wine group. The AUC(0-t), significantly decreased of tolbutamide in raw, processed with rice-wine and processed with salt-water groups.
  
  
  CONCLUSIONS
  The raw Phellodendri Cortex can inhibit CYP1A2, induce CYP3 A4 and also is need to make a further research work on CYP2C9 and CYP2E1. Meanwhile, it also can change the activities of cytochrome P450 after processed with rice-wine and salt-water. The Phellodendri Cortex processed with rice-wine can reduce the inhibitory effect of CYP1A2 and enhance induction of CYP3A4, it provides reference and basis to make an interpretation about Phellodendri Cortex processed with rice-wine.
authors.forename: Peng-peng
authors.initials: PP
authors.lastname: Liu
authors.forename: Tian-zhu
authors.initials: TZ
authors.lastname: Jia
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2; D065609:Cytochrome P-450 CYP1A2 Inhibitors / Q000737:chemistry*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065701:Cytochrome P-450 CYP3A Inducers / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D003580:Cytochromes / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D032102:Phellodendron / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D014920:Wine
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065701:Cytochrome P-450 CYP3A Inducers; D003580:Cytochromes; D020033:Protein Isoforms; D012965:Sodium Chloride; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A