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314554 tn?1337457719

Extent RIBA prolongs half-life of Pegasys and Peg Intron?

I realize this is a frequently addressed topic – but I am trying to get this straight in my mind; so, here goes:

Given:
1) Due to it's longer and branched-chain PEG, Pegasys has a half-life ("terminal elimination") of 50-80 hours.

2) Whereas, due to it's shorter and linear-chain PEG, Peg Intron has a half-life of 30-50 hours. (Note that NPIA or non-pegylated interferon alfa has a half-life of only 3-5 hours.)

3) …multiple-dose ribavirin half-life (298 hours) is considerably longer than the single-dose half-life (79 hours)

Questions:
#1  What extent does RIBA prolong the half-life of the Pegasys and the Peg Intron?
#2  Am I phrasing the question right? Is this how it works?
#3  If so, is this the reason (*in some cases*) it helps to increase the dose of RIBA : to get more oomph out of the Pegasys and/or Peg Intron?

If #3 is accurate, then is this why deviating (e.g. missing a dose) from the RIBA dosing schedule might be counter productive (for lack of a better word)?


Info came from here:
Differences between Pegasys and Peg Intron http://www.janis7hepc.com/differences_between_pegasys_and.htm

Clinical Pharmacology of Ribavirin
http://journal.medscape.com/viewarticle/416602_2
9 Responses
Avatar universal
If so, is this the reason (*in some cases*) it helps to increase the dose of RIBA : to get more oomph out of the Pegasys and/or Peg Intron?
---------------
Forgive the analogy, but like women, riba works in mysterious ways and anyone who says they understand the mechanism is an amateur :) We do know that riba plays a very important role both in viral response and SVR (cure) but as to "how" and "why", that is still up for grabs although lots of theories abound using some very technical language.

-- Jim
Avatar universal
why deviating (e.g. missing a dose) from the RIBA dosing schedule might be counter productive (for lack of a better word)?
--------------------------------------------------------
Credible evidence suggests that the key to riba dosing is keeping serum riba levels up, something unfortunately isn't directly tested for in this country, or most anywhere except under study or lab conditions. In light of this, missing a single dose of riba may have some effect on those serum riba levels although one should also keep in mind that riba has a very long half life which should mitigate that effect to some degree although some of us -- and I include myself here -- were quite fastidious about making sure no doses were missed and those missed were quickly compensated for.

More important is making sure you are properly dosed as best as possible. Per protocols, you want to first make sure you are on a proper weight-based dose -- and not a flat 800 mg -- regardless of genotype. Second, you and your doctor might then want to track your hemoglobin response weekly during the early part of treatment from baseline. If you don't see your hemoglobin move down a couple of points by let's say week 3, then an increase in dose might be discussed. Especially if the viral response isn't up to par. Such a strategy would also involve weekly viral load testing from week one until UND.

-- Jim
314554 tn?1337457719
Thanks for giving my question the the good ol' college try despite the awkward wording.
Probably I need a few of the basics before I proceed. I was curious about the RIBA and PEG pharmacokinetics, not about the RIBA dosing schedule per se.

I'm betting my understanding defies the principals of pharmacokinetics.
The RIBA does not necessarily prolong the half-life of the PEG; rather, since RIBA has little prolonged antiviral benefit on it's own, the relationsip between the PEG and RIBA might be..synergistic....and I wanted to know the extent.
.

k

Avatar universal
My main point is that the pharmacokinetics of riba aren't fully understood and all you are left with are varying theories -- i.e. they really don't know why riba works.
314554 tn?1337457719
OK.   This thread took a wrong turn. Sorry for coming of as an as*hole.
The thing is *you* and a few others very likely DO know what I was curious about and I was reluctant to come out and ask.

I did this with the RIBA at week 12 and with the PEG at end of week 17.

The Q's about half-lives and the extent RIBA prolongs the PEG.    
Here is why I asked:

I had a VL test last Friday (week 18)  to determine whether I am UND. I am out of PEG although I have a courtesy shot at the doctor's office if I need it. My GI is unconcerned and doesn't think I need the shot since it is unlikely I will be UND.  I  am unconcerned as well since my VL only went from 5.995 down to 3.89  and back up to 4.11.

The week or so before I had the VL test to determine whether I proceed with treatment I upped my RIBA, did a Peg shot on Thursday morning, did another late Sunday night, another on Thursday morning and had the labs done on Friday afternoon.   This is a lot of PEG and RIBA in a short time period but I figured "what the hey," since I did this at week 12 with the RIBA and it worked. The doctor's office will call after the holiday with the results of the blood test.

I did pick up the courtesy shot for Thursday night and am still doing the RIBA (1200).
I fell ok despite all the PEG. I'm not sure whether the PEG (three redipens) in the short time frame will have made a difference.

What think you?
Reckless, I don't mind since I'm goin' down swinging.
Counter productive???

k


Avatar universal
Several issues going on.

First, skipping a Peg shot -- or more than one -- is never a good idea no matter how much riba you take. Unless, of course, you have to skip  a shot for good medical reasons.

Second, if I read you correctly, what you appeared to have done is to more or less double-dosed the Peg one week and upped the riba. Many have done similar with a doctor on board, but usually the double-dosing was earlier in treatment.

Third, you took your viral load test the day after your Peg shot which could give you a false UND.  In other words, the blood for the viral load test is usually drawn the day *before* the injection to give you a more conservative 'trough" value.

I'm also unclear why they are pulling you off treatment now, as opposed to at week 12 or week 24 which are the two usual bench marks.  

As a slow responder, just barely making a two-log drop at week 12 -- and also considering you only have stage 1 liver damage -- a reasonable decision might have been to stop treatment and wait for better drugs. That would have been my choice.

On the other hand, someone with a different take on treatment risks versus rewards might urge you to continue to week 24 to see if you are UND -- and if so, then treat for 72 weeks total.

Perhaps your doc took an in between view or perhaps with the viral load curve going up they decided a week 24 UND wasn't going to happen.

As I mentioned, personally I would have stopped at week 12 -- but if your intent is to get UND by week 24, then raising both the riba and Peg (with your doc's approval of course) seems reasonable. You could also look into adding Alinia or some IR drugs (if relevant) although again, I personally would call it a day with these drugs.

Lastly, if you do continue on, try and get tested the day before your injection to get a more realistic viral load reading.

-- Jim
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