What does "5-FU clearance" mean? Re: Xeloda

[zephyr]

I should be able to figure this out but I'm stumped. I found a Medscape article about Xeloda that states:

During the first cycle of capecitabine development, three concomitant drugs were found to affect 5-FU clearance. Paracetamol and morphine increased 5-FU clearance by 26% and 41%, respectively, and loperamide decreased 5-FU clearance by 31%

Paracetamol is the European version of Tylenol. It works better on me than Tylenol so I brought home several boxes a few months ago. That said, the two are claimed to be identical so the "clearance" issue might apply to Tylenol too. Loperamide, as many of us know all too well, is Imodium. Before I take either one, would someone please translate the quoted sentence for me?

Thanks.

[mpbser]

I believe that the term essentially means "to be gotten rid of" i.e. " to clear" the body. For chemo to be "gotten rid of" within the body, it is via metabolism and excretion (out through the kidneys -- pee!). Here is an article I looked at to see if I am on the right track: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375329/

[zephyr]

I believe that the term essentially means "to be gotten rid of" i.e. " to clear" the body. For chemo to be "gotten rid of" within the body, it is via metabolism and excretion (out through the kidneys -- pee!). Here is an article I looked at to see if I am on the right track: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375329/

Thanks, you are correct. I just found another explanation here:
https://www.nottingham.ac.uk/nmp/sonet/rlos/bioproc/clearance1/index.html

Interesting that paracetamol (and maybe Tylenol) increased clearance but loperamide decreased clearance. Presumably an increased clearance would result in less toxicity but how does that play out for efficacy? Back to research...

[Rock_Robster]

Hi mpbser, I found the ‘Pharmacokinetics’ section of the below article very helpful for my understanding of how Xeloda works in the body, particularly the Capecitabine —> DFCR —> DFUR —> 5FU cascade. Also the relationship (or lack of) between plasma concentration levels and tumour concentration levels:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484526/

[GrouseMan]

Increased clearance could result in less effectiveness of the 5-FU and Decreased clearance could contribute to increased side effects. One should not mess around with these variables in drug phamacokinetics. Both these drugs effect 5-FU clearance by either increasing or decreasing metabolism by liver enzymes responsible for breaking down compounds in the body for elimination. How 5-FU is dosed was optimized to minimize side effects and maximize effectiveness. So Anything that effects this is not a good thing.

Regards,

GrouseMan