HERBeDRUG INTERACTIONS 425
volunteers[122, 123]. Indeed, there has been conflicting evidence provided by studies assessing the role of ginkgo in affecting drug metabolism.
Contrary to case reports mentioned earlier, a small randomized controlled study
concluded thatGingko bilobadid not enhance clopidogrel antiplatelet activity[124]. Another
small randomized controlled study reported no significant changes to plasma concentrations
of warfarin enantiomers and clotting status in healthy subjects taking ginkgo for 7 days[125].
Given that CYP2C9 metabolizes warfarin, it is worth noting that levels of tolbutamide and
diclofenac, which are metabolized by this enzyme, were not affected after ginkgo administration in healthy individuals [126]. Furthermore, a clinical study determined that CYP1A2,
CYP2D6, CYP2E1 and CYP3A4 activities were not affected in healthy volunteers given
Gingko bilobafor 28 days [19]. A later study demonstrated that ginkgo induced CYP2C19,
reduced the bioavailability of omeprazole and increased the production of its hydroxylated
metabolites[127]. Indeed, a case report described fatal seizures and subtherapeutic levels of
phenytoin, which is separately metabolized by CYP2C9 and CYP2C19, in an individual selfmedicating with ginkgo[128]. A recent clinical study demonstrated that diazepam (another
CYP2C19 substrate) metabolism was unaffected in healthy subjects taking ginkgo extracts
HERBeDRUG INTERACTIONS 425
volunteers[122, 123]. Indeed, there has been conflicting evidence provided by studies assessing the role of ginkgo in affecting drug metabolism.
Contrary to case reports mentioned earlier, a small randomized controlled study
concluded thatGingko bilobadid not enhance clopidogrel antiplatelet activity[124]. Another
small randomized controlled study reported no significant changes to plasma concentrations
of warfarin enantiomers and clotting status in healthy subjects taking ginkgo for 7 days[125].
Given that CYP2C9 metabolizes warfarin, it is worth noting that levels of tolbutamide and
diclofenac, which are metabolized by this enzyme, were not affected after ginkgo administration in healthy individuals [126]. Furthermore, a clinical study determined that CYP1A2,
CYP2D6, CYP2E1 and CYP3A4 activities were not affected in healthy volunteers given
Gingko bilobafor 28 days [19]. A later study demonstrated that ginkgo induced CYP2C19,
reduced the bioavailability of omeprazole and increased the production of its hydroxylated
metabolites[127]. Indeed, a case report described fatal seizures and subtherapeutic levels of
phenytoin, which is separately metabolized by CYP2C9 and CYP2C19, in an individual selfmedicating with ginkgo[128]. A recent clinical study demonstrated that diazepam (another
CYP2C19 substrate) metabolism was unaffected in healthy subjects taking ginkgo extracts
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