Tier 4 — mechanistic

Effects of quercetin on the bioavailability of doxorubicin in rats: role of CYP3A4 and P-gp inhibition by quercetin

Choi JS, Piao YJ, Kang KW
Archives of Pharmacal Research 2011 34(4):607-613

Bibliography

PubMed
PMID 21544726
Funding
Not reported in the available abstract/metadata.
Competing interests
Not reported in the available abstract/metadata.

Study snapshot

DesignControlled animal pharmacokinetic study
ModelRats (oral and intravenous doxorubicin, with and without co-administered quercetin)
SampleNot specified in available metadata
InterventionOral quercetin co-administered with oral or IV doxorubicin
DurationSingle-dose pharmacokinetic study
EndpointsDoxorubicin plasma AUC; Oral bioavailability; CYP3A4 inhibition; P-glycoprotein-mediated efflux

What the study showed, in plain terms

This rat study tested whether quercetin, a flavonoid closely related to fisetin, changes how much of the chemotherapy drug doxorubicin gets absorbed into the bloodstream. Quercetin inhibited two things doxorubicin depends on for normal clearance — an enzyme called CYP3A4 and a transporter called P-glycoprotein — and this raised oral doxorubicin levels substantially, by roughly 30% to more than double depending on the dose. Doxorubicin given directly into a vein was not affected, showing this is specifically an absorption effect. It is not a fisetin study, but it illustrates that this class of flavonoid can meaningfully change how much of a co-administered drug reaches the bloodstream — relevant context for thinking about fisetin and CYP3A4-metabolised medications, even though fisetin itself has not been tested this way.

Key findings

Co-administered quercetin increased oral doxorubicin's plasma AUC by approximately 31% to 136% and relative bioavailability by 1.32- to 2.36-fold in a dose-dependent manner, through CYP3A4 and P-glycoprotein inhibition. Intravenous doxorubicin pharmacokinetics were unaffected, localising the effect to first-pass absorption.

What this study can and cannot tell us

Animal model only, no human data. Studies quercetin, not fisetin — the two are related flavonoids but not identical, and fisetin's own CYP3A4/P-gp interaction potency has not been directly measured this way. Doxorubicin is a narrow-therapeutic-index drug, so this finding may not generalise to drugs with wider safety margins.

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