And given the number of people on aspirin these days for their heart disease it is a very common medication.
Lately however I have been doing a lot of pharmacogenomic testing and the PPIs can be a right royal PITA as they inhibit CYP2C19. That can interfere with the antidepressants or benzodiazepines that I may need to prescribe for mental health purposes.
Here is a list of CYP2C19 inhibitors:
dothiepin
fluconazole
fluvoxamine
isoniazid
modafinil
omeprazole
ticlopidine
voriconazole
cimetidine
fluoxetine
ketoconazole
lansoprazole
rabeprazole
sertraline
The ones in red tend to be the main inhibitors. So giving someone omeprazole rather than rabeprazole has the potential to be a problem especially when they need a lot of fine tuning.
So which are the current worst?
Drug Metab Dispos. 2012 Sep;40(9):1698-711. doi: 10.1124/dmd.112.045575. Epub 2012 May 30.
Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19.
Zvyaga T, Chang SY, Chen C, Yang Z, Vuppugalla R, Hurley J, Thorndike D, Wagner A, Chimalakonda A, Rodrigues AD.
Abstract
Six proton pump inhibitors (PPIs), omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, and rabeprazole, were shown to be weak inhibitors of cytochromes P450 (CYP3A4, -2B6, -2D6, -2C9, -2C8, and -1A2) in human liver microsomes. In most cases, IC₅₀ values were greater than 40 μM, except for dexlansoprazole and lansoprazole with CYP1A2 (IC₅₀ = ∼8 μM) and esomeprazole with CYP2C8 (IC₅₀ = 31 μM). With the exception of CYP2C19 inhibition by omeprazole and esomeprazole (IC₅₀ ratio, 2.5 to 5.9), there was no evidence for a marked time-dependent shift in IC₅₀ (IC₅₀ ratio, ≤ 2) after a 30-min preincubation with NADPH. In the absence of preincubation, lansoprazole (IC₅₀ = 0.73 μM) and esomeprazole (IC₅₀ = 3.7 μM) were the most potent CYP2C19 inhibitors, followed by dexlansoprazole and omeprazole (IC₅₀ = ∼7.0 μM). Rabeprazole and pantoprazole (IC₅₀ = ≥ 25 μM) were the weakest. A similar ranking was obtained with recombinant CYP2C19. Despite the IC₅₀ ranking, after consideration of plasma levels (static and dynamic), protein binding, and metabolism-dependent inhibition, it is concluded that omeprazole and esomeprazole are the most potent CYP2C19 inhibitors. This was confirmed after the incubation of the individual PPIs with human primary hepatocytes (in the presence of human serum) and by monitoring their impact on diazepam N-demethylase activity at a low concentration of diazepam (2 μM). Data described herein are consistent with reports that PPIs are mostly weak inhibitors of cytochromes P450 in vivo. However, two members of the PPI class (esomeprazole and omeprazole) are more likely to serve as clinically relevant inhibitors of CYP2C19.
Omeprazole is also known as Losec and is approved for GORD.
Esomeprazole or Nexium is also approved for GORD.
Lansoprazole or Zoton is approved for GORD
Pantoprazole or Somac is approved for GORD
Rabeprazole or Pariet is approved for GORD
Why am I interested in this stuff?
I have a patient who has CYP2C19 *17 so is a heterozygous rapid metaboliser and who is on polypharmacy. That means he metabolises things about 25% faster. Maximum serum levels tend to occur about 2.5 hours after dosing. The pantoprazole gets metabolised in the liver then 80% of the metabolites pass via the kidneys with the remainder ending up in faeces.
The halflife of the metabolites which are not clinically effective is about 1.5 hours.
Now my patient is an old bloke. His renal function and hepatic function is okay at the moment but I don't want to stress the system if I can avoid it. However the once daily dosing should be fine with no risk of accumulation especially being a rapid metaboliser.
Flicking through the PI, it also pays to watch B12 which I routinely check anyway in this age group.
So it looks like pantoprazole shouldn't be too much of a problem and of the PPIs is one of the better ones to be on.
