I am looking at giving our senior dog something like Denamarin, a liver supplement, which contains an active part of an extract from milk thistle called Silybin, to aid in improving liver health.
I will of course talk to our vet before doing so, but am I correct from my reading that this can inhibit the metabolism of a range of drugs, because of it's effect on the CYP3A4 and CYP2C9 enzymes?
To my understanding CYP3A4 is used by a lot of drugs, and particularly prednisone, and if it is inhibited by Silybin, the drug cannot be converted to its active form, prednisolone, and if given consistently, can build up in the body?
We have Pred-X on hand, which we give on the off chance our dog gets stung by a bee (she is allergic), to give us time to get to the vet - however, to my understanding this is the activated form, prednisolone.
Given it's already the active form, this doesn't present a major issue with making sure it works, and in time, however, if I am correct, the body still needs to metabolise it so that it's broken down for elimination?
On that, if I am also correct, whilst CYP3A4 would be the primary enzyme to do this, there are also multiple backup systems for processing drugs, and the drug elimination process doesn't completely stop; it just becomes slower and relies more on alternative pathways?
Assuming this is all true, in this example scenario it wouldn't present much of an issue, as it was a one off dose of Pred-X, in it's already active state, and it will be broken down by the body and eliminated, just at a slower rate.
Again, assuming this is all true, my main concern then becomes if we need to give other drugs. To my understanding, I believe the half-life of Silybin is around 6 hours, however the effects can last 3-7 days whilst the enzymes recover.
Denamarin seems to use a special formulation, silybin-phosphatidylcholine complex, which is covered in this study, run by the company behind it.
The study showed that:
- The phosphatidylcholine complex dramatically increased absorption, creating what the paper described as a 3-4.4 fold increase in bioavailability
- Helps it get into the bloodstream more effectively
- Dogs given the phosphatidylcholine complex showed significantly higher blood levels compared to regular silymarin extract
- The complex achieved peak concentrations (Cmax) of about 1310 ng/mL
- Regular silymarin extract only reached peak concentrations of about 472 ng/mL
- The overall exposure (AUC) was about 3 times higher with the complex
- The complex seems to maintain therapeutic levels longer than standard milk thistle extract, though it still follows a similar elimination pattern through the liver.
Now, whilst this sounds all good for the therapeutic effect, this raises increased concerns for the potential effects on the metabolism of other drugs.
However, I do note that, and I will be contacting Denamarin about this, but they state in their FAQ that:
Can Denamarin be used with other products? Yes, your veterinarian may recommend combining Denamarin with other products, and/or dietary modifications. There are no known interactions of Denamarin with drugs or other supplements.
So, my questions are, do I have this all correct?
- Should I be concerned about drug inhibition?
- Could this potentially cause a build up in the body of drugs?
- Does the body need to break down the drugs via the same enzymes for elimination?
- Are there "backup systems/enzymes" available if the main enzymes are inhibited?
- If stopping Silybin, do the enzymes need 3-7 days to recover?
- Does it seem like Denamarin's formulation may make my concerns even more valid?
