Steven and others
According to the paper you have posted on PPI's, it would appear in their research anyway, that lansoprazole is superior to omeprazole (I understand the potential lack of efficacy crossing the BBB). We are currently using omeprazole 60 mg bid around the time of TMZ use.
My questions:
Is there any reason to believe we should switch to lansoprazole based on this paper?
Omeprazole has been shown to improve the efficacy of DCA. Is there any information suggesting this activity is unique to omeprazole, or is it more likely a class effect of the drug?
What are people dosing lansoprazole at?
Thank you!
For reference I think we're talking about these two studies.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/26018420
http://www.ncbi.nlm.nih.gov/pubmed/22740984
The first study showed that lansoprazole was superior to other PPIs at equimolar concentrations in several different cell lines in vitro (including U87 GBM cells). To put this into perspective though, the minimum concentration used was 50 micromolar. Max plasma concentrations of omeprazole or lansoprazole tend to be in the single-digit micromolar range, and 97% of that is bound to plasma proteins.
The in vivo part of the study is more convincing, but of course this is a single xenografted melanoma mouse model. Would these findings hold up in other models? Or in an intracranial glioma model?
The other paper (on DCA + omeprazole) is exceptionally short (3 pages) and doesn't attempt to explain the observed synergy between DCA and omeprazole other than to say "As described, DCA and OMP are thought to inhibit tumor
cell growth through the common pathway of ROS production
by influencing the intracellular pH levels" in the study introduction.
My guess is that we're looking at a class effect, but my central question about PPIs and glioma is to what extent do they cross the BBB? There are no human studies on this that I've seen, and the rodent studies tell us that a small amount crosses. My guess is that PPIs have very limited activity when the BBB is intact, but may have some effect when the BBB is disrupted (ie for contract-enhancing tumor). This is all speculation of course.
Another benefit of proton pump inhibitors is a reduced risk for ulcers in people taking NSAIDs including COX-2 inhibitors.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/16494585
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