Journal article
Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice
Pharmaceutical research, Vol.41(3), pp.557-566
03/01/2024
PMID: 38302834
Abstract
Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34-43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene's solubility as the responsible mechanism.
The effects of green tea extract, (-)-epigallocatechin gallate (EGCG), and (-)-epigallocatechin (EGC) on raloxifene's solubility were assessed in fasted state simulated intestinal fluids (FaSSIF) and fed state simulated intestinal fluids (FeSSIF). EGCG and EGC represent green tea's main bioactive constituents, flavan-3-gallate and flavan-3-ol catechins respectively, and the tested concentrations (mM) match the µg/mg of each compound in the extract. Our mouse study (n = 5/time point) evaluated the effect of green tea extract and EGCG on the systemic exposure of raloxifene.
EGCG (1 mM) and EGC (1.27 mM) decreased raloxifene's solubility in FaSSIF by 78% and 13%, respectively. Micelle size in FaSSIF increased with increasing EGCG concentrations (> 1000% at 1 mM), whereas EGC (1.27 mM) did not change micelle size. We observed 3.4-fold higher raloxifene solubility in FeSSIF compared to FaSSIF, and neither green tea extract nor EGCG significantly affected raloxifene solubility or micelle size in FeSSIF. The mice study showed that green tea extract significantly decreased raloxifene C
by 44%, whereas EGCG had no effect. Green tea extract and EGCG did not affect the AUC
of raloxifene or the metabolite-to-parent AUC ratio.
This study demonstrated flavan-3-gallate catechins may decrease solubility of poorly water-soluble drugs such as raloxifene, particularly in the fasted state.
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Details
- Title
- Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice
- Creators
- Victoria O Oyanna - Washington State University SpokaneBaron J Bechtold - Washington State University SpokaneKatherine D Lynch - Washington State University SpokaneM Ridge Call - Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, 412 E. Spokane Falls Blvd, Spokane, WA, 99202, USATyler N Graf - Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USANicholas H Oberlies - Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USAJohn D Clarke - Washington State University, Department of Pharmaceutical Sciences
- Publication Details
- Pharmaceutical research, Vol.41(3), pp.557-566
- Academic Unit
- Department of Pharmaceutical Sciences
- Grant note
- U54 AT008909 / NCCIH NIH HHS U54AT008909 / NCCIH NIH HHS R21AT011101 / NCCIH NIH HHS R21 AT011101 / NCCIH NIH HHS
- Identifiers
- 99901181237301842
- Language
- English
- Resource Type
- Journal article