Cytochrome P450 and p-glycoprotein drug ... - Dr. Jeffrey Fudin

WARFARIN

Liver/Gut Metabolism

Free warfarin in blood, INR=2.5

WARFARIN-2C9 COMPLEX

2C9

ENZYME

Figure 1

© RxPrep/Dr. Jeffrey Fudin

WARFARIN

RIFAMPIN

Rifampin is a 2C9 inducer encouraging more 2C9 production


Less free warfarin in blood due to more enzymes from rifampin induction of 2C9, INR = 1.1


2C9

ENZYME

Figure 2


WARFARIN

AMIODARONE

Amiodarone is a 2C9 inhibitor discouraging 2C9 production


More free warfarin in blood due to less metabolism from amiodarone inhibition of 2C9, INR = 4.8


2C9

ENZYME

Figure 3


CODEINE

+

2D6 ENZYME

=

MORPHINE

Codeine is a prodrug requiring activation to morphine for analgesic activity in the liver prior to being released into blood. This requires conversion metabolism by 2D6 enzymes.


Morphine is readily available due to 2D6 metabolism of codeine

Figure 4


PAROXETINE

CODEINE

+

2D6 ENZYME

≠

MORPHINE

Paroxetine inhibits production of 2D6 enzymes which precludes the conversion of codeine to morphine


Codeine only is available now due to inhibited production of 2D6, no morhine and minimal analgesia.

Figure 5


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pGP

OUT

$FMM .FNCSBOF

IN

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Figure 6
