How does phenobarbital "stimulate" CYP2C19?

[aced126]

Apparently if you take phenobarbital and warfarin together (both metabolised by 2C19), the warfarin loses its effectiveness because it gets metabolised by the enzyme more.

I would've thought the phenobarbital would act as an inhibitor of 2C19 (as well as the warfarin acting as an inhibitor) and that both drugs would potentiate one another. Apparently this is not the case; can anyone explain this in more depth?

 

[knockout]

I'm not a pharmacist but I guess warfarin also metabolises on CYP2C9
(According to this paper also metabolises through much much more enzymes then this two Link: https://www.pharmgkb.org/pathway/PA145011113 )
If we view from this viewpoint, from my best knowledge ( Link: http://www.ncbi.nlm.nih.gov/pubmed/14600250 ) phenobarbital is CYP2C9 inducer so probably it could cause the higher metabolism rate of warfarin. But as I written I'm not specialist, so if I was wrong feel free to correct me.

knockout

 

[Kittycat5]

Knockout is exactly correct on PB being an enzyme inducer. It is one of the classic drugs taught to be so. It also is a quite broad inducer, inducing CYP 2C9, 3A4, 1A2 and others. Several, if not all listed above, are involved in warfarin metabolism, so care must be used when adding PB to a patient stable on Coumadin. Dose increases of as much as 60% are not unheard of as well as extra vigilant INR monitoring.

 

[serotonin2A]

Are you asking why barbiturates upregulate Cytochrome P450?

1. Barbiturates stimulate ALA synthase, which increases porphyrin synthesis.
2. Porphyrin is converted to heme
3. Heme is a component of cytochrome P450 enzymes