Bioavailability and pharmacokinetic studies of eurycomanone from Eurycoma longifolia.
A validated HPLC analysis of eurycomanone (1), a bioactive quassinoid, in rat plasma following oral and intravenous administration of Eurycoma longifolia Jack extract was developed for pharmacokinetic and bioavailability studies. Relatively high plasma eurycomanone concentrations were detected after an intravenous injection of 10 mg/kg extract F2 containing 1.96 mg/kg of the quassinoid. However, it declined rapidly to zero after 8 h. Its mean elimination rate constant (k(e)), biological half-life (t(1/2)), volume of distribution (V(d)) and clearance (CL) were 0.88 +/- 0.19 h (-1), 1.00 +/- 0.26 h, 0.68 +/- 0.30 L/kg and 0.39 +/- 0.08 L/h/kg, respectively. Following oral administration of eurycomanone, its Cmax and Tmax values were detected as 0.33 +/- 0.03 microg/mL and 4.40 +/- 0.98 h, respectively. The plasma concentration of the quassinoid after oral administration was much lower than after intravenous application in spite of the oral dose being 5 times higher. The results indicate that eurycomanone is poorly bioavailable when given orally. A comparison of the AUC (0-->infinity) obtained orally to that obtained after an intravenous administration (normalized for dose differences) revealed that the absolute bioavailability of the compound was low with 10.5 %. Furthermore, the compound appeared to be well distributed in the extravascular fluids because of its relatively high V(d) value. The poor oral bioavailability was not attributed to instability problems because eurycomanone has been shown to be stable under different pH conditions. Thus, its poor oral bioavailability may be due to poor membrane permeability in view of its low P value and/or high first-pass metabolism.
Low
Bin-Seng
BS
School of Pharmaceutical Sciences, University Sains Malaysia, Penang, Malaysia.
Ng
Bee-Hong
BH
Choy
Wai-Peng
WP
Yuen
Kah-Hay
KH
Chan
Kit-Lam
KL
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D035701:Eurycoma; D007275:Injections, Intravenous; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018517:Plant Roots; D036702:Quassins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010936:Plant Extracts; D036702:Quassins; C506425:eurycomanone