Pharmacokinetics of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol and its active metabolite after oral and intravenous administration in rat

Abstract

The pharmacokinetics behaviour of 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol (25-OCH3-PPD) and its active metabolite after oral and intravenous administration in rats were studied. Rats were administered 2.5, 5.0, and 10 mg kg(-1) 25-OCH3-PPD orally after an overnight fasting or by intravenous injection of 5 mg kg(-1) 25-OCH3-PPD via the tail vein. Plasma concentration-time profiles of 25-OCH3-PPD and its active metabolite 25-O-demethylated (25-OH-PPD) in rats were monitored by liquid chromatography-tandem mass spectroscopy (HPLC-MS-MS). The 25-O-demethylated metabolite appears to be a pathway in the phase I metabolism of 25-OCH3-PPD in rats. The plasma concentration of the metabolite was higher than that of the parent compound.

25-Methoxyl-Dammarane-3β, 12β, 20-Triol, A Ginseng Saponin Derivative and an Anticancer Agent: In Vitro and In Vivo Activities, Molecular Mechanism of Action, Pharmacokinetics and Structural Modification

“…The 25-O-demethylated metabolite appears as a pathway in the phase I metabolism of 25-OCH 3 -PPD in rats; it was shown that the absolute bioavailability of 25-OCH 3 -PPD was approximately 19.7% and the drug-time curve of 25-OCH 3 -PPD exhibited distinct double-peaks after oral administration. In addition, the apparent distribution volume and plasma clearance of 20(R)-and (S)-25-OCH 3 -PPD was significantly different [23,24]. The low oral bioavailability and rapid reduction of 25-OCH 3 -PPD in the blood indicated that formulation modification was required.…”

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

“…The selection of a suitable self-emulsifying formulation requires assessment of the solubility of the compound in various components, the area of the self-emulsifying region as obtained in the pseudoternary phase diagrams, and the droplet size distribution of the subsequent self-emulsification. 15 25-OH-PPD is the main active phase 1 metabolite of 25-OCH 3 -PPD, 16,17 and was found to induce cell cycle arrest in G1 phase in H838 and H358 lung cancer cell lines in a dose-dependent manner. 18 In that experiment, 25-OH-PPD was studied simultaneously with 25-OCH 3 -PPD.…”

Determination of 20(R)-25-Methoxyl-dammarane-3,12,20-triol and Its Active Metabolite in Beagle Dog Plasma by LC–MS–MS and Its Application to Pharmacokinetics Studies

“…20(R)-25-Methoxyl-dammarane-3,12,20-triol (25-OCH 3 -PPD) was an aglycone of PPD-containing ginsenosides. The study showed that 25-OCH 3 -PPD could be metabolized to 20(R)-dammarane-3,12,20,25-tetrol (25-OH-PPD) after oral administration of 25-OCH 3 -PPD [5].…”

“…They also both inhibited the growth of xenograft tumors without any host toxicity [9] and showed greater growth inhibition than Rg 3 [6,10]. Since the structure of PPD-containing ginsenosides had no chromophore, LC-MS-MS was a prime candidate for analysis [5,[11][12][13][14][15][16][17][18][19]. LC-MS-MS method has been developed in previous study for the assay of 25-OCH 3 -PPD in rat [5].…”

“…Since the structure of PPD-containing ginsenosides had no chromophore, LC-MS-MS was a prime candidate for analysis [5,[11][12][13][14][15][16][17][18][19]. LC-MS-MS method has been developed in previous study for the assay of 25-OCH 3 -PPD in rat [5]. And an optimized method using LC-MS was validated for determining 25-OH-PPD in rat plasma [16].…”