Bioavailability and Pharmacokinetic Studies of Eurycomanone fromEurycoma longifolia

Abstract

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.

Reverse Phase High Performance Liquid Chromatography for the Quantification of Eurycomanone in <i>Eurycoma longifolia</i> Jack (Simaroubaceae) Extracts and their Commercial Products

“…The use of acetonitrile at 10 % and 0.1 % formic acid at 90 % resulted in short elution time (< 20 min), and eurycomanone retention time was 5.6 min while maintaining high resolution of several compounds in the extracts. The LOD and LOQ values indicated high sensitivity of the method; these values were comparable to those reported in previous methods for quantification of E. longifolia compounds [14]. This method can be applied in quantification of eurycomanone in aqueous extracts of the root and those prepared in organic solvents.…”

“…Therefore, E. longifolia products must be standardized to comply with the set standards in order to protect consumers from possible toxic effects. Few methods are available for standardization of E. longifolia extracts or commercial products including a RP-HPLC for analysis of eurycomanone in serum for pharmacokinetics [14], and HPLC for determination of 9-methoxycanthin-6-one, 3-methylcanthin-5,6-dione and its 9-methoxy analogue in E. longifolia Jack [15], and HPLC for determination of 9-methoxycanthin-6-one in plasma for pharmacokinetics [16], and HPLC method for determination of various compounds in E. longifolia extracts [17]. Increased demand for E. longifolia as a result of its aphrodisiac properties, the availability of more than 200 products [6] and eurycomanone's toxicity require quantification of eurycomanone.…”

Review on Eurycoma longifolia Pharmacological and Phytochemical Properties

“…The result showed that the compound is better absorbed if administered intravenously than orally. Low et al (2005) discovered the same result in their studies on the bioavailability and pharmacokinetics of eurycomanone in rat plasma following oral and intravenous administration. Higher plasma concentration of eurycomanone was detected after intravenous injection than oral administration despite the oral dose was 5 times higher.…”

Effects of Eurycoma Longifolia on Fracture Healing of Androgen-Deficient Osteoporosis Model: A Micro Computed Tomograph Analysis

“…The effect of EL was not significantly captured by micro-CT. Orchidectomised rats may not be a suitable model to determine the effects of EL. One of the mechanisms to increase testosterone by EL is by elevating the luteinizing hormone (LH) and follicle stimulating hormone (FSH), which would stimulate the Leydig cells to produce testosterone in testes (Low et al 2005). Since the rat's testes were removed in this model, the EL's testosterone-raising effect through this mechanism was not available.…”