8 replies to this topic

[mdszj]

All

I take 100 mg Sprycel at dinner, so far seems to be working with no major problems.  However, past 3-4 days I have had the runs a few hours after dinner, possibly because I have a cold or gut bug or something at the moment.  There seems to be a cold or something going around in my area.  Was just wondering how long it takes for Sprycel to get absorbed by the stomach etc.  Hopefully it gets absorbed quickly before everything gets eliminated.  Would the effective dosage get reduced if you have diarrhea?

Any info appreciated thx Mike.

[hannibellemo]

Hi, Mike,

I'm also on Sprycel. This might help answer your question. http://www.mayoclini...-system/an00896 (I couldn't get the link to work, you may need to cut and paste).

According to the Mayo clinic the average time for food to go through the digestive process is 53 hours. What you are eliminating shortly after dinner is probably not what you just put in your mouth! Unless you have serious diarrhea several times a day, there should be no cause for alarm.

Pat

[Trey]

TKI drug absorption starts almost immediately in the stomach and within an hour or so most of it has been absorbed.  It continues to be absorbed along the intestines, but there is never full uptake.  Once Sprycel is taken up into the bloodstream it stays a shorter period than the other TKI drugs:

Half-life of TKI drugs:

Sprycel: 5 hours

Tasigna:  17 hours

Gleevec: 18 hours

Bosulif: 22 hours (Bosutinib)

Iclusig: 24 hours  (Ponatinib)

But it is not the absorbed drug that causes the diarrhea.  It is the response by the intestinal wall to the drug that causes the diarrhea, probably off-target kinase inhibition (maybe c-Kit and others).  So diarrhea can start within a few hours of taking the drug.

[mdszj]

Pat and Trey

thx for the info - both responses addressed different pieces of the puzzle.  Based on both of your input, sounds like there was likely no problem with lack of tki chemical during those few days, which are now over. 

I knew Sprycel solubility is highly dependent on pH.  When I was first dx'd I spent every waking moment researching all kinds of stuff.  I remember (hopefully correctly) I came across a research paper that indicated there is several orders of magnitude difference in sprycel solubility, depending on what pH range you are at, with stomach acid being at the low end of the pH range, where Sprycel is much more soluble.  I have not been able to re-locate that doc though, too bad.

OK, on to the next side effect!!

[Tedsey]

Could you tell me more about what you learned about the solubility/absorption of Sprycel?  I am also on 100mg.  I was on G and I heard that it needs an acidic environment, but I cannot remember if the drug needs this acidic environment to be absorbed or broken down (solubility).  What I am most concerned about is what would increase the body's ability to absorb Sprycel (curcumin aside).  For example, I heard that calcium, or drinking Gleevec with milk may interfere with the Gleevec's absorption.  And ascorbic helps Gleevec's absorption.  Glad things are back to normal for you.

Thanks,

Tedsey

[mdszj]

Hi Tedsey 

I just did another search for the paper and found it:

http://www.ema.europ...WC500056995.pdf

Look on page 2 at the top, section called Active Substance - it states:

"Dasatinib is a crystalline white powder and exhibits pH dependent aqueous solubility (from 18.4

mg/ml at pH 2.6 to 0.008 mg/ml at pH 6.0). It is very slightly soluble in acetone and acetonitrile and

slightly soluble in ethanol, methanol, polyethyleneglycol 400 and propyleneglycol. It is practically

insoluble in corn oil."

So, dividing 18.4 mg/ml (at pH 2.6) by 0.008 mg/ml (at pH 6) gives 2300.  So at pH of 2.6, 2300 times as much dasatinib is solubilized compared to pH of 6.  But I am not sure where this paper came from or who put it together (no author, company, etc)

This article says stomach pH varies from a pH of 1-2 up to 4-5, depending on whether you eat or not, etc.

http://chemistry.abo.../Stomach-Ph.htm

This one says stomach pH goes from 1.5 to 3.5

http://en.wikipedia....ki/Gastric_acid

So it looks like stomach acid is at the low pH range which should hopefully dissolve it easily.

I thought I read somewhere that taking calcium decreases absorption.  But I did not read anything about effects of milk - I hope not because I always drink milk, including during dinner when I take my pill.

Hope this helps, Mike

[OhRose]

Interesting conversation. My question is, what makes it better for absorption? What helps the stomach acid? Should you eat with taking the meds? Do any certain types of food promote acid for absorption? I seem to have plenty of acid most nights when I want to sleep   I take my sprycel med of 70mg between 8-9 pm.  Thanks

[Trey]

T,

All TKI drugs require an acidic environment for proper absorption, so Sprycel is definitely affected by stomach acidity.  For instance, studies have shown that taking an antacid along with Sprycel reduces absorption by up to 60%.  Because of this, I would take it with a Vit C (ascorbic acid) if wanting to maximize absorption (which is what I did with Gleevec and it worked quite well for me).

http://onlinelibrary...enticated=false

Also, high fat foods eaten with the drugs promote absorption. 

So maybe Vit C and pork rinds?????

The Sprycel dosing sheet contains the following:

http://www.sprycel.c...ng-sprycel.aspx

SPRYCEL^® (dasatinib) is best absorbed from your stomach into your bloodstream in the presence of stomach acid. You should avoid taking medicines that reduce stomach acid, such as:

Tagamet^® (cimetidine)
Pepcid^® (famotidine)
Zantac^® (ranitidine)
Prilosec^® (omeprazole)

Protonix^® (pantoprazole sodium) 
Nexium^® (esomeprazole)
AcipHex^® (rabeprazole)
Prevacid^® (lansoprazole)

Medicines that neutralize stomach acid, such as Maalox^® (aluminum hydroxide/magnesium hydroxide), Tums^® (calcium carbonate), or Rolaids^® (calcium carbonate and magnesia), may be taken up to 2 hours before or 2 hours after SPRYCEL.

[mdszj]

Seems like any type of acidic food should help dissolve it.  I like what Trey said about taking vitamin c with your dinner, which I am going to start doing tonight.   I also use olive oil and white vinegar when I eat salads, that should help too.   I may also lay off the milk at dinner just in case that helps to neutralize acid.