Journal article
Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes
Planta medica, Vol.77(3), pp.265-270
02/2011
Handle:
https://hdl.handle.net/2376/106524
PMCID: PMC3023844
PMID: 20717876
Abstract
Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic
in vitro-in vivo
approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, a cranberry juice inhibited intestinal first-pass midazolam metabolism.
In vitro
studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [
Vaccinium macrocarpon
Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC
50
) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and <10 μM, respectively, using HIM as the enzyme source and was 2.8, 4.3, and <10 μM, respectively, using recombinant CYP3A4 as the enzyme source. These
in vitro
inhibitory potencies, which are within the range of those reported for two CYP3A inhibitory components in grapefruit juice, suggest that these triterpenes may have contributed to the midazolam-cranberry juice interaction observed in the clinical study.
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Details
- Title
- Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes
- Creators
- Eunkyung Kim - Herbal Medicinal Products Division, Korea Food and Drug Administration, Seoul, 122-704, Republic of KoreaArlene Sy-Cordero - Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC 27402, USATyler N Graf - Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC 27402, USAScott J Brantley - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAMary F Paine - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USANicholas H Oberlies - Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC 27402, USA
- Publication Details
- Planta medica, Vol.77(3), pp.265-270
- Academic Unit
- Pharmaceutical Sciences, Department of
- Identifiers
- 99900546812001842
- Language
- English
- Resource Type
- Journal article