Pharmacological Properties of Galenical Preparation. XV. Pharmacokinetics Study of Evocarpine and Its Metabolite in Rats

• Published in: Chemical & pharmaceutical bulletin Vol. 39; no. 11; pp. 3064 - 3066
• Main Authors: KANO, Yoshihiro, CHEN, Xue-Fen, KANEMAKI, Satoru, ZONG, Qing, KOMATSU, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1991; Maruzen
• Subjects: 5-hydroxy-1, 4-dihydro-2-quinolin-2-yl pentanoic acid; Animals; Biological and medical sciences; Biotransformation; evocarpine; Evodia fruit; Evodia officinalis; General pharmacology; Male; Medical sciences; metabolite; Pharmacognosy. Homeopathy. Health food; pharmacokinetic parameter; Pharmacology. Drug treatments; Quinolones - metabolism; Quinolones - pharmacokinetics; Rats; Rats, Inbred Strains; Rutaceae; Asia; China; Rat; Metabolite; Rodentia; Rutaceae; Oral administration; Quinoline derivatives; Medicinal plant; Vertebrata; Alkaloid; Mammalia; Folk medicine; Dicotyledones; Animal; Angiospermae; Plant origin; Spermatophyta; Pharmacokinetics
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.39.3064

It is known that when methanol extract of Evodia fruit is orally administered, 5-(1, 4-dihydro-1-methyl-4-oxo-2-quinolin-2-yl) pentanoic acid (EVCA) is excreated as a matabolite in rat urine. In this study, we separated Evodia fruit extract into major alkaloids administered each alkaloid individally to male Wistar rats. Consequently, it was demonstrated that the original substance of the metabolite are evocarpine and its analogues, dihydroevocarpine and 1-methyl-2-undecenyl-4(1H)-quinolone. Investigation of a blood sample after oral administration of evocarpine by high performance liquid chromatography confirmed that the substance was absorbed without alteration.Pharmacokinetics of evocarpine after intravenous injection was expressed in a one-compartment model, showing a linear elimination of plasma evocarpine up to a dosage of 75 mg/kg. Total plasma clearance (CL), volume of distribution (Vd), and half-life (T1/2) of evocarpine were 60 ml/min·kg, 3.2l /kg and 0.6 h-1, respectively. Metabolic ratio of evocarpine into EVCA after intravenous injection was 15.4%, and absorption ratio of the unaltered compound calculated from the levels of AUC after oral administration and intravenous injection was 4.7%. In this paper, it is shown that evocarpine is absorbed amount 100% when it is administered orally.