Transcript or S-warfarin

Drug X
S-warfarin
Agents that DECREASE metabolism
(inhibit or compete for cytochrome P450)
are more important than those that
increase metabolism
Drug X
R-warfarin and
S-warfarin
Must also consider that both forms of
warfarin can interact with other drugs
Both inhibitors and substrates of a
particular CYP isozyme decrease the
metabolism of substrates of that isozyme
 increased efficacy
Inducers increase the metabolism of
substrates  decreased efficacy
For example, for CYP 2C9, both amiodarone and
carvedilol will increase the efficacy of celecoxib, but
barbiturates will reduce it
In other words, drugs in the inhibitor and
inducer columns can affect drugs in the
substrate column, but substrates don’t
affect inhibitors and inducers
Substrates can affect other substrates
Taking up the case of warfarin, the
active enantiomer is S-warfarin which
is metabolized by CYP 2C9.
That means we have to be most
concerned by drugs that inhibit CYP
2C9 ---- i.e., amiodarone, cimetidine,
etc., and especially fluvoxamine.
We also have to worry about drug
interactions where warfarin causes
an adverse drug interaction with
another drug.
Drug X
S-warfarin
Drug X
R&S-warfarin
Neither warfarin enantiomer is an
inducer or an inhibitor of CYP enzymes.
So the drugs that could interact are ones
that are substrates for the CYP isozymes
that EITHER R- or S-warfarin is a
substrate of. So you could expect
interactions with amitriptyline, carvedilol,
amitriptyline and alfentanil (reading just
the first drug in the substrate list for each
affected isozyme)