Pharmacokinetics of Dehydroevodiamine Following Intravenous Administration in Rats

  • Kim, Seong-Yun (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Moon, Chan-Soo (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Choi, Yun-Sik (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sang-Bok (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
  • Published : 2004.02.21


Dehydroevodiamine (DHED) is one of the bioactive components of the Chinese herbal medicine Wu-chu-yu-tang that has been shown to produce various pharmacological effects. In the present study, we investigated the pharmacokinetics of DHED after intravenous administration of two doses (2.5 and 5 mg/kg) in anesthetized rats. The plasma concentration of DHED was measured by reverse-phase high-performance liquid chromatography with UV detection. The mean area under the curve of the time-concentration profile was $21.9\;and\;53.9\;{\mu}g{\cdot}min/ml$ after the 2.5- and 5-mg/kg doses, respectively, and the volume of distribution was 1584.9 and 1580.6 ml following 2.5- and 5-mg/kg doses, respectively. Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. The terminal elimination half-life was $91.8{\pm}16.6\;min$ and $78.7{\pm}11.9\;min$ in the dose of 2.5 and 5 mg/kg, respectively. This is the first report to study the pharmacokinetics of DHED in animals.


  1. Chiou WF, Liao JF, Chen CF. Comparative study of the vasodilatory effects of three quinazoline alkaloids isolated from Evodia rutaecarpa. J Nat Products 59: 374-378, 1996
  2. Haji A, Momose Y, Takeda R, Nakanishi S, Horiuchi T, Arisawa M. Increased feline cerebral blood flow induced by dehydroevodiamine hydrochloride from Evodia rutaecarpa. J Nat Products 57: 387-389, 1994
  3. Tsai TH, Lee TF, Chen CF, Wang LC. Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and febrile rats. Biochem Behav 50: 293-298, 1995
  4. Ueng YF, Don MJ, Peng HC, Wang SY, Wang JJ, Chen CF. Effects of Wu-chu-yu-tang and its components herbs on drug-metabolizing enzymes. Jpn J Pharmacol 89: 267-273, 2002
  5. Loh SH, Lee AR, Huang WH, Lin CI. Ionic mechanism responsible for the antiarrhythmic action of dehydroevodiamine in guineapig isolated cardiomyocytes. Br J Pharmacol 106: 517-523, 1992
  6. Park CH, Choi SH, Kim CH, Seo JH, Koo JW, Rah JC, Kim HS, Jeong SJ, Joo WS, Lee YJ, Kim YS, Kim MS, Suh YH. General pharmacology of indole [2',3' : 3,4] pyrido [2,1-b] quinazolinium-5, 7, 8, 13-tetrahydro-14-methyl-5-oxo-chloride, a new antidementia agent. Arzneimittelforschung 53: 393-401, 2003
  7. Kiangsu Institute of Modern Medicine. Encyclopedia of Chinese Drugs, Shanghai Scientific and Technical Publication. Shanghai, p1118-1120, 1977
  8. Kano Y, Zong Q, Komatsu K. Pharmacological properties of Galenical preparation. XIV. Body temperature retaining effect of the Chinese traditional medicine, "Goshuyu-to" and component crude drugs. Chem Pharm Bull (Tokyo) 39: 690-692, 1991
  9. Wang HH, Chou CJ, Liao JF, Chen CF. Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice. Eur J Pharmacol 413: 221-225, 2001
  10. Peng YT, Shum AY, Tasi TH, Lin LC, Chen CF. High-performance liquid chromatography of the quinazolinocarboline alkaloid dehydroevodiamine. J Chromatogr 617: 87-93, 1993
  11. Park CH, Kim SH, Choi W, Lee YJ, Kim JS, Kang SS, Suh YH. Novel anticholinesterase and antiamnesic activities of dehydroevodiamine, a constituent of Evodia rutaecarpa. Planta Med 62: 405-409, 1996
  12. Chen CF, Chen SM, Lin MT, Chow SY. In vivo and in vitro studies on the mechanism of cardiovascular effect of Wu-Chu-Yu (Evodiae Fructus). Am J Chin Med 9: 39-57, 1981
  13. Park CH, Lee YJ, Lee SH, Choi SH, Kim HS, Jeong SJ, Kim SS, Suh YH. Dehydroevodiamine. HCl prevents impairment of learning and memory and neuronal loss in rat models of cognitive disturbance. J Neurochem 74: 244-253, 2000
  14. Yang MC, Wu SL, Kuo JS, Chen CF. The hypotensive and negative chronotropic effects of dehydroevodiamine. Eur J Pharmacol 182: 537-542, 1990