title: The Effects of Rheum palmatum L. on the Pharmacokinetic of Major Diterpene Alkaloids of Aconitum carmichaelii Debx. in Rats.
abstract: OBJECTIVE
  Aconitum carmichaelii Debx. (Fuzi) is usually compatible with Rheum palmatum L. (Dahuang) in clinic. The study is conducted to investigate the influence of Dahuang on the pharmacokinetics of Fuzi.
  
  
  METHODS
  Twelve rats were randomly divided into two groups. Fuzi group was orally administered a single dose of 38.4 mg/kg total alkaloids from Fuzi, and Fuzi-Dahuang group was given 38.4 mg/kg total alkaloids from Fuzi and 76.8 mg/kg Dahuang anthraquinones at the same time. The plasma concentrations of aconitine (AC), mesaconitine (MC), and hypaconitine (HC), benzoylaconine (BAC), benzoylmesaconine (BMC), benzoylhypaconine (BHC), and aconine (ACN) were determined by ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry method. The pharmacokinetic parameters were calculated including maximum plasma concentration (Cmax), area under the plasma concentration-time curve in all time-points (AUClast), apparent volume of distribution (Vz/F), apparent plasma clearance (CL/F), elimination half-life (T1/2), and time to achieve maximum concentration (Tmax).
  
  
  RESULTS
  AUClastof diester diterpene alkaloids (DDAs) were 58.20, 169.78, 278.48 ng·h/mL for AC, MC, and HC in Fuzi-Dahuang group which were remarkably lower than that in Fuzi group (71.62, 183.13, 410.59 ng·h/mL for AC, MC, HC). CL/F was significantly increased from 173.88 to 218.85 mL/h for AC, 433.22 to 800.21 mL/h for MC, 1150.61 to 1307.30 mL/h for HC after combination. However, with the significantly increased Cmax, AUClastof monoester diterpene alkaloids (MDAs) and amine diterpenoid alkaloids (ADAs) were 152.42, 1238.95, 287.96, 123.33 ng·h/mL for BAC, BHC, BMC, ACN in Fuzi-Dahuang group which were remarkably higher than that in Fuzi group (54.47, 1105.48, 200.75, 86.48 ng·h/mL for BAC, BHC, BMC, ACN). At the same time, CL/F was significantly decreased from 1030.15 to 607.09, 3594.06 to 1437.54, 1441.23 to 1310.14, and 391.30 to 239.50 mL/h for each one after combination.
  
  
  CONCLUSIONS
  Fuzi diterpene alkaloids pharmacokinetics was greatly influenced by Dahuang which may account for the compatibility mechanism of effect-enhancing and toxicity-reducing.
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China.
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Li
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China.
authors.forename: Meng-Jie
authors.initials: MJ
authors.lastname: Zhao
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China.
authors.forename: An
authors.initials: A
authors.lastname: Yuan
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Gong
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China.
authors.forename: Meng-Jun
authors.initials: MJ
authors.lastname: Zhao
authors.affiliation: Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China. pengchengsub@126.com.|The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, People's Republic of China. pengchengsub@126.com.|State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 611137, People's Republic of China. pengchengsub@126.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
mesh_terms: D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000493:pharmacokinetics*; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004224:Diterpenes / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D041743:Herb-Drug Interactions / Q000502:physiology; D008297:Male; D010936:Plant Extracts / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000009:adverse effects*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000470:Alkaloids; D000880:Anthraquinones; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C575009:fuzi drug herbal