Hello again Dori.
I wouldn’t EVER want to discourage milk thistle use in totality. I really do believe in it’s potent powers to protect and even help heal the liver. But it’s also because of these potent powers I think awareness/caution is warranted, and especially in regards to possible interactions with other drugs/botanicals, and under certain other circumstances.
I think the last time I looked into this, was well over a year ago. The bookmarks I had on it died with my last computer. It’s hard to get detailed and reliable info from anywhere but the manufacturers, as to actual expected half lives, exactly how the drugs are metabolized, etc. and am having difficulty getting that reliable info again. It’s also hard to get reliable studies on various herbs and supplements,
Going by other resources I think it can be established that ivermectin is primarily metabolized by CYP3A4 in the liver, and as far as I’m concerned, for me, there is enough evidence that milk thistle does inhibit CYP3A4, even though there are few studies as to exactly what extent, dosage rates, potency hard to be determined etc. on milk thistle or almost other botanicals/herb. Most sites I’ve seen, classify milk thistle as a CYP3A4 inhibitor of undefined potency, which would be usually be the case in unregulated and essentially non-standardized supplements. That study referenced in the link i posted the other day, implies relatively high inhibiting potency for milk thistle.
http://www.hcvadvocate.org/hepatitis/hepC/mthistle.html
Not sure exactly how milbemycin, moxidectin, is metabolized, but I would have to assume it’s much the same way as ivermectin, as they are all in the same class of drugs. Apparently ivermectin has a longer longer half life in dogs than i recalled, and milbemycin a little longer than ivermectin. But these, when given in oral dosages, are at least predictable as to their peak plasma concentrations, especially when given without a meal, it’s within hours. Because of the slowed release method of topical moxidectin, peak concentration times for that cannot reliably be determined, I’ve read anywhere between 8 to 21 days after dosage. I would have liked to have incorporated milk thistle into Turbo’s regimen at some point, but as of now, I don’t see how i can confidently do that using moxidectin, and what i don’t know yet about moxidectin. Because all these HWP’s are in the same class of drugs, for now I have to assume they are metablized much in the same way as ivermectin.
If a medication has an expected half life of 24 hours, it doesn’t mean the medication will be cleared in 48 hours. It means that every 24 hours the remaining plasma concentration should be expected to be divided by 2.
I suspect that most advice for milk thistle is for very low dosage, only once a day, and after a reasonably safe time period, at least a day or two after HWP administration? Given in that way, I wouldn’t think there would be significant alterations in elimination time or efficacy, However, I wouldn’t listen to any advice that says to give it before, concurrently with, or immediately after any HWP. Nor any loading up on dosage of it. Additional precautions should be dogs with the defective/suspected defective MDR1 gene, which are already much more susceptible to these drugs crossing the blood/brain barrier, dogs on certain other drugs, or are being given high doses of ivermectin, or the others.
“Dogs with defects in the P-glycoprotein gene (MDR1) can be severely poisoned by ivermectin.”
“Since drugs that inhibit CYP3A4 enzymes often also inhibit P-glycoprotein transport, the risk of increased absorption past the blood-brain barrier exists when ivermectin is administered along with other CYP3A4 inhibitors. These drugs include statins, HIV protease inhibitors, many calcium channel blockers, and glucocorticoids such as dexamethasone, lidocaine, and the benzodiazepines.[21]”
http://en.wikipedia.org/wiki/Ivermectin
Note: I think ivermectin and other like drugs given in the low dosages as given normally for heartworm protection, are usually considered safe for dogs with the defective MDR1 gene, unless other factors come into play.
The only time I would ever consider loading up on milk thistle for a dog is if poisonous mushroom ingestion is strongly suspected or in acute aflatoxin poisoning. In which case, high dosages could save the dogs liver and it’s life.
