Abstract
Kaempferia parviflora (KP) is an herbal plant in the family of Zingiberaceae. KP mainly contains methoxyflavones, especially 5,7-dimethoxyflavone (DMF), 5,7,4′-trimethoxyflavone (TMF), and 3,5,7,3′,4′-pentamethoxyflavone (PMF). The present study was designed to characterize the pharmacokinetics, including bioavailability, distribution, excretion, and identification of metabolites after administration of a KP ethanolic extract. Male rats were orally or intravenously administered a 250 mg/kg concentration of a KP extract, and blood samples were obtained at selected times to determine pharmacokinetic parameters of PMF, TMF, and DMF. For distribution and excretion studies, the organs, urine, and feces samples were collected at various times after oral administration of a larger (750 mg/kg) dose of KP extract. Methoxyflavones in the biological samples were quantified by high-performance liquid chromatography-UV, and the metabolites in urine and feces were further identified by using liquid chromatography-tandem mass spectrometry. After oral administration, concentrations of the three methoxyflavones quickly approached their maximal concentration, ranging from 0.55 to 0.88 μg/ml within 1 to 2 h after administration, and then were gradually excreted with half-lives of 3 to 6 h. The methoxyflavones showed low oral bioavailability of 1 to 4%. Three methoxyflavones were detected at their highest levels in liver followed by kidney. They were also found in lung, testes, and brain. After absorption, organ distribution, and metabolism, the components of KP were mainly eliminated through urine in the forms of demethylated, sulfated, and glucuronidated products and as demethylated metabolites in the feces. The parent compounds were found to have 0.79, 1.76, and 3.10% dose recovery in urine and 1.06, 1.77, and 0.96% dose recovery in feces for PMF, TMF, and DMF, respectively. These studies are the first to describe the pharmacokinetics of KP extract to provide the information on blood and tissue levels.
Footnotes
This research was supported in part by the National Research Council of Thailand [Grants 2552-117 and 2554RPCS52045]; the Royal Golden Jubilee Ph.D Program, the Thailand Research Fund, Thailand [Grant PHD/0072/2549]; the Khon Kaen University's Graduate Research Fund Academic Year 2011, Thailand [Grant 53212105]; and Center for Research and Development of Herbal Health Products, Khon Kaen University, Thailand.
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
ABBREVIATIONS:
- KP
- Kaempferia parviflora
- PMF
- 3,5,7,3′,4′-pentamethoxyflavone
- TMF
- 5,7,4′-trimethoxyflavone
- AUC
- area under the blood concentration-time curve
- DMF
- 5,7-dimethoxyflavone
- HPLC
- high-performance liquid chromatography
- LC-MS
- liquid chromatography-mass spectrometry
- AUC
- area under the curve
- LC-MS/MS
- liquid chromatography-tandem mass spectrometry
- LOD
- limit of detection
- LOQ
- limit of quantitation.
- Received June 9, 2012.
- Accepted September 7, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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