التفاصيل البيبلوغرافية
| العنوان: |
Absorption, Metabolic Stability, and Pharmacokinetics of Ginger Phytochemicals. |
| المؤلفون: |
Mukkavilli, Rao1 vmukkavilli@gsu.edu, Chunhua Yang1 ychnjcpu@gmail.com, Tanwar, Reenu Singh1 drreenu10@gmail.com, Ghareeb, Ahmed1 afghareeb80@gmail.com, Luthra, Latika1 latika.luthra@yahoo.com, Aneja, Ritu1 raneja@gsu.edu |
| المصدر: |
Molecules. Apr2017, Vol. 22 Issue 4, p553. 13p. 1 Diagram, 8 Charts, 3 Graphs. |
| مصطلحات موضوعية: |
*ANTINEOPLASTIC agents, *METABOLISM, *PHARMACOKINETICS, *GINGER, *PHYTOCHEMICALS, *LIQUID chromatography-mass spectrometry |
| مستخلص: |
We have previously demonstrated promising anticancer efficacy of orally-fed whole ginger extract (GE) in preclinical prostate models emphasizing the importance of preservation of the natural "milieu". Essentially, GE primarily includes active ginger phenolics viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogaol (6S). However, the druglikeness properties of active GE phenolics like solubility, stability, and metabolic characteristics are poorly understood. Herein, we determined the physicochemical and biochemical properties of GE phenolics by conducting in vitro assays and mouse pharmacokinetic studies with and without co-administration of ketoconazole (KTZ). GE phenolics showed low to moderate solubility in various pH buffers but were stable in simulated gastric and intestinal fluids, indicating their suitability for oral administration. All GE phenolics were metabolically unstable and showed high intrinsic clearance in mouse, rat dog, and human liver microsomes. Upon oral administration of 250 mg/kg GE, sub-therapeutic concentrations of GE phenolics were observed. Treatment of plasma samples with β-glucuronidase (βgd) increased the exposure of all GE phenolics by 10 to 700-fold. Co-administration of KTZ with GE increased the exposure of free GE phenolics by 3 to 60-fold. Interestingly, when the same samples were treated with βgd, the exposure of GE phenolics increased by 11 to 60-fold, suggesting inhibition of phase I metabolism by KTZ but little effect on glucuronide conjugation. Correlating the in vitro and in vivo results, it is reasonable to conclude that phase II metabolism seems to be the predominant clearance pathway for GE phenolics. We present evidence that the first-pass metabolism, particularly glucuronide conjugation of GE phenolics, underlies low systemic exposure. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder