triclabendazole resistance...biochemistry questions.. need help.. c p450 inhibitors..
I have been trying to find reasons how or why the fasciola trematodes can create a resistance to the triclabendazole.
There seem to be some studies that improve the efficiency of egaten when it is coupled with a c p450 inhibitor, especially with resistant fasciola species.
Here is the abstracts I was looking at. It's odd that most of them written by the same researchers. But, the other two seem to have the same conclusions.
http://www.ncbi.nlm.nih.gov/pubmed?term=ketoconazole%20%20ticlabendazole
Here is another interesting article about mono oxygenase and it's role in metabolizing the triclabendazole. It seems the inhibitors can keep the triclabendazole inside the fluke longer preventing it from being metabolized into something else. This seems promising.
Here are some other articles on mono oxygenase.
http://www.ncbi.nlm.nih.gov/pubmed/16669866
http://www.ncbi.nlm.nih.gov/pubmed/10509757
Also, grapefruit juice can inhibit the p glycoprotein as well. I just don't know if it would interact with the egaten.
Compound alpha appeared to treat fasciolosis very well. Except I don't know how to make it.
Also, bromelain inhibited a portion of the p450 enzymes as well. The cyp2c9 sequence which appears to have a large role in oxidizing the pollutants as well.
http://www.ncbi.nlm.nih.gov/pubmed?term=bromelain%20p450
http://en.wikipedia.org/wiki/CYP2C9
I wonder if this will help some of the other meds work better as well?
David