title: Comparative pharmacokinetics and bioavailability of four alkaloids in different formulations from Corydalis decumbens.
abstract: BACKGROUND
  Corydalis decumbens, a Traditional Chinese Medicine listed in Chinese Pharmacopoeia, is clinically used for the treatment of paralytic stroke, headache, rheumatic arthritis and sciatica in China.
  
  
  OBJECTIVE
  This study was aimed to compare the pharmacokinetics and bioavailability of protopine, tetrahydropalmatine, bicuculline, and egenine in three formulations prepared from the rhizomes of Corydalis decumbens.
  
  
  METHODS
  Alkaloid extract (CDAs-SFE) was prepared from the rhizomes of Corydalis decumbens by supercritical CO2 fluid extraction; CDAs-SFE/HPβCD (hydroxypropyl-β-cyclodextrin inclusion complex), and CDAs-SFE/HCl (hydrochloride freeze-dried powder) were resulted from CDAs-SFE through complexation with HPβCD and hydrochloride, respectively. An UFLC-MS/MS method was developed for quantitative analysis of protopine, tetrahydropalmatine, bicuculline and egenine simultaneously in rat plasma after oral administration. The differences of pharmacokinetics and bioavailability of the four alkaloids in three formulations were determined by pharmacokinetics analyses.
  
  
  CONCLUSIONS
  The Cmax, AUC and bioavailability of protopine and tetrahydropalamatine (bioactive components) in CDAs-SFE/HCl were significantly higher than in CDAs-SFE and in CDAs-SFE/HPβCD. In contrast, in CDAs-SFE/HPβCD, AUC and bioavailability of tetrahydropalamatine were significantly lower, while those of bicuculline (toxic compound) appeared to be higher than both in CDAs-SFE and in CDAs-SFE/HCl. The results indicated that CDAs-SFE/HCl was the best beneficial formulation among the three formulations for the alkaloid extract prepared from the rhizomes of Corydalis decumbens, in which protopine and tetrahydropalamatine displayed higher bioavailability, but lower for bicuculline.
authors.affiliation: State Key Laboratory of New Drug & Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, 1320 West Beijing Road, Shanghai 200040, China. czw1962@126.com
authors.forename: Chunzhen
authors.initials: C
authors.lastname: Wu
authors.forename: Renjie
authors.initials: R
authors.lastname: Yan
authors.forename: Rongjin
authors.initials: R
authors.lastname: Zhang
authors.forename: Fan
authors.initials: F
authors.lastname: Bai
authors.forename: Yifang
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wu
authors.forename: Anming
authors.initials: A
authors.lastname: Wu
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002681:China; D002851:Chromatography, High Pressure Liquid; D031311:Corydalis / Q000737:chemistry*; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D020834:Ethnopharmacology; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D027343:Rhizome / Q000737:chemistry; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal
keywords: Bicuculline; Bioavailability; CDAs; CDAs-SFE.; CDAs-SFE/HCl; CDAs-SFE/HCl freeze-dried powder; CDAs-SFE/HPβCD; CDAs-SFE/HPβCD inclusion complex; Corydalis decumbens alkaloids; Corydalis decumbens alkaloids by supercritical CO(2) fluid extraction; Egenine; GAP; Good Agriculture Practices; HPβCD; LD(50); Pharmacokinetics; Protopine; SFE; TCM; Tetrahydropalmatine; Traditional Chinese Medicine; UFLC–QTrp-MS/MS; hydroxypropyl-β-cyclodextrin; medium lethal dose; supercritical CO(2) fluid extraction; ultra-fast liquid chromatography–triple quadrupole linear ion trap mass spectrometry