is well known that the cytochrome (CYP) P450 enzyme system is involved in drug
metabolism of many medications used in clinical practice and have been
implicated in the causing clinically relevant drug-drug interactions.1,2
There are a number of CYP450 enzymes involved in mediating drug interactions
and commonly include CYP1A2, 2C9, 2C19, 2D6, and 3A4.1 Of these CYP
enzymes, CYP3A4 is not only the most prevalent CYP enzyme in the liver, but is
used by more than 50% of medications on the market for their metabolism and
elimination from the body.1 If the number and level of complexity were
not enough with prescription medications alone, the addition of a growing
increase in the use of natural and herbal medicines, which are now known to
inhibit CYP enzymes as well, is only going to make it worse.3 In fact,
the number of herbal or natural medicines that are known to inhibit CYP3A4 is
growing and is of clinical importance when assessing the potential etiologies
in adverse drug events that appear to be from a drug-drug interaction (see the
table below).4-14 As such, all clinicians, regardless of specialty or
level of training, need to be aware of the list natural medicines found in the
table provided at EBM Consult.
To see the online drug and herbal reference table for inhibitors of CYP3A4 .... Click Here
is evident from the table that most of these herbal products appear to directly
inhibit the activity of CYP3A4 instead of influencing the gene transcription.4-14
In addition, many appear to be mechanism-based inhibitors.
Mechanism-based inhibition of CYP3A4 can be an inhibition or inactivation of
existing CYP3A4 via the formation of a metabolite intermediate complex.
This can be an important form of inhibition since it can result in the
irreversible inhibition of CYP3A4 in a concentration and time-dependent
manner. As such, medications depending on the activity and presence of
functional CYP3A4 enzyme may then not be metabolized until the body turns on
gene transcription to make more of the enzyme. Since the effect of gene
transcription is not acute, it could take days to regenerate the needed CYP3A4
enzyme to metabolize the accumulating medication. This can obviously put
the patient at significant risk for drug related side effects and/or
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H, Tezuka Y, Kadota S et al. Identification and characterization of
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