Aa
Hepatitis Researcher, Pre-Dosing Ribavirin
I am starting treatment with Infergen in 2 weeks and am planning on pre-dosing riba(1,600 daily) leading up to the start date. Do you feel this may give me an edge or would it be better to just add the extra riba to the daily intake once I start the Infergen?
willingquote: “I can see a "priming-the-pump" argument, that one doesn't reach the therapeutic dose for the first one or two weeks. However it seems you are suggesting something else entirely, that one's system somehow needs to "warm-up" to riba's effect, and as far as I know there's no support for such an effect.”
Yes, I’m suggesting there may be and probably is at least some form of phase lag between the increasing riba serum levels and the (apparent) immuno-modulative effects it has on the body. Of course if the serum levels are increased very slowly, then the phase lag is probably negligible. But if the serum levels ramp up very quickly (as you’ve suggested), then I would suspect there would be a lag between riba-referred immuno-modulation and serum concentration. It does not seem reasonable to expect the body to respond near instantaneously to these referred effects (should they exist, of course). And yes, I believe you’re correct in suggesting there’s “no support for such an effect.” But using my amazing powers of deductive logic, that’s my story and I’m stickin’ to it. ;-) Also, as an anecdotal aside, I tinkered with my riba dose constantly during my own tx. I could see and feel this postulated phase lag both in my side effect profile and in my labwork.
willingquote: “If such an effect existed, wouldn't it simply affect the optimal total drug duration?”
Not sure I understand what you’re saying here, but if it did simply affect optimal total drug dose duration (by shortening it), wouldn’t that we a worthwhile objective? And assuming you buy into the importance of RVR (within the context of SOC), and assuming (for the moment) pre-dosing riba is an effective strategy for achieving RVR, then wouldn’t it be important to have the riba-referred immuno-modulative effects fully (or largely) engaged prior to commencing IFN dosing? And since RVR (or ultra-RVR) imparts the possibility of both truncated treatment AND enhanced odds of achieving SVR, then I would think the assertion that this strategy would “simply affect the optimal drug duration” might be a bit overly simplistic.
willingquote: “Obviously nearly all of the SVRs in the world managed to reach that state even without steady-state concentrations of riba for their first couple of weeks.”
True, but a fairer question might be “how many people in the world did not achieve RVR and were subsequently denied their SVR as a consequence of not pre-dosing ribavirin?”
willingquote: “re the TVR/SOC combo strategy you brought up the other day, if it's taken more than 10 years to simply figure out riba dosages, how long do you think it'll take to figure out how to optimally combine tvr, r1626, ntz and soc?”
Agreed, the combinatrix of the possible drugs, their dosages and when to take each drug is growing exponentially. It’ll be interesting to see how things develop as time goes on, especially in regards to the staggered PI dosing mentioned for that particular 28 week boceprevir group.
Yes, I’m suggesting there may be and probably is at least some form of phase lag between the increasing riba serum levels and the (apparent) immuno-modulative effects it has on the body. Of course if the serum levels are increased very slowly, then the phase lag is probably negligible. But if the serum levels ramp up very quickly (as you’ve suggested), then I would suspect there would be a lag between riba-referred immuno-modulation and serum concentration. It does not seem reasonable to expect the body to respond near instantaneously to these referred effects (should they exist, of course). And yes, I believe you’re correct in suggesting there’s “no support for such an effect.” But using my amazing powers of deductive logic, that’s my story and I’m stickin’ to it. ;-) Also, as an anecdotal aside, I tinkered with my riba dose constantly during my own tx. I could see and feel this postulated phase lag both in my side effect profile and in my labwork.
willingquote: “If such an effect existed, wouldn't it simply affect the optimal total drug duration?”
Not sure I understand what you’re saying here, but if it did simply affect optimal total drug dose duration (by shortening it), wouldn’t that we a worthwhile objective? And assuming you buy into the importance of RVR (within the context of SOC), and assuming (for the moment) pre-dosing riba is an effective strategy for achieving RVR, then wouldn’t it be important to have the riba-referred immuno-modulative effects fully (or largely) engaged prior to commencing IFN dosing? And since RVR (or ultra-RVR) imparts the possibility of both truncated treatment AND enhanced odds of achieving SVR, then I would think the assertion that this strategy would “simply affect the optimal drug duration” might be a bit overly simplistic.
willingquote: “Obviously nearly all of the SVRs in the world managed to reach that state even without steady-state concentrations of riba for their first couple of weeks.”
True, but a fairer question might be “how many people in the world did not achieve RVR and were subsequently denied their SVR as a consequence of not pre-dosing ribavirin?”
willingquote: “re the TVR/SOC combo strategy you brought up the other day, if it's taken more than 10 years to simply figure out riba dosages, how long do you think it'll take to figure out how to optimally combine tvr, r1626, ntz and soc?”
Agreed, the combinatrix of the possible drugs, their dosages and when to take each drug is growing exponentially. It’ll be interesting to see how things develop as time goes on, especially in regards to the staggered PI dosing mentioned for that particular 28 week boceprevir group.
like you said this is "old news" and even though most of us know the dangers of riba we know there is nothing else that will "cure" this disease at the present time. actually the riba scares me more then the interferon. the bad things that these tx drugs can do to you is something that we elect not to discuss that often. most likely because reading the facts just makes you feel worse so we kinda never bring it up.
COPEGUS (Ribavirin, USP) can be extremely harmful and cause birth defects in an unborn baby. Female patients and the female partners of male patients should avoid getting pregnant. Ribavirin is known to cause anemia (low red blood cells), which can make heart disease worse. Also, ribavirin can harm your DNA and possibly cause cancer (see medication guide for more information and warnings).
Who should not take PEGASYS and COPEGUS?
Do not take PEGASYS alone or with COPEGUS if:
You are pregnant or your partner is pregnant
You or your partner plans to get pregnant during therapy or within 6 months after treatment ends
You are breastfeeding
You have hepatitis caused by your immune system (autoimmune hepatitis)
You have unstable or severe liver disease before or during treatment
You are allergic to alpha interferons or any of the ingredients in PEGASYS and COPEGUS
You have abnormal red blood cells (caused by conditions like sickle-cell anemia or thalassemia major)
The most serious side effects of PEGASYS and COPEGUS are:
Risks to pregnancies
Mental health problems (such as irritability, depression, anxiety, aggressiveness, trouble with drug addiction or overdose, thoughts about suicide, suicide attempts, suicide and thoughts about homicide)
Blood problems (like a drop in blood cells leading to increased risk for infections, bleeding and/or heart or circulatory problems)
Infections (which sometimes cause death)
Lung problems (like trouble breathing, pneumonia)
Eye problems (like blurred vision, loss of vision)
Autoimmune problems (such as psoriasis, thyroid problems)
Heart problems (including chest pain and, rarely, a heart attack)
Liver problems (rarely, liver function worsens). Patients with both the hepatitis C virus and HIV can have an increased chance of having liver failure during PEGASYS treatment. Change in a blood test that measures liver inflammation occurs more often in patients with hepatitis B. If you have a rise in this blood test you may need to be watched more closely with additional blood tests.
http://www.pegasys.com/
the best treatment available has the possibilities/disclaimer of affecting/destroying/damaging many other systems inside the body.
COPEGUS® (Ribavirin, USP), which you also may have heard of by its generic name, ribavirin, is a medication that is used in combination with PEGASYS to help fight the hepatitis C virus. COPEGUS is taken in the form of several tablets every day.
Although COPEGUS cannot fight hepatitis C on its own, studies have shown that it does help PEGASYS work better. The precise reason why this combination of drugs works well is not clear. What is known is that COPEGUS interferes with the reproduction of the hepatitis C virus in many ways—one way is by causing mistakes to be made when the genetic material of the virus is being copied during reproduction. For viruses to survive in your body, they need to reproduce quickly. Interrupting that process helps your body fight off the attack.
Since all medications can cause side effects, it's possible that you could experience side effects while taking PEGASYS alone or in combination with COPEGUS. If you have any questions about your treatment, be sure to speak with your healthcare professional.
COPEGUS can be extremely harmful and cause birth defects in an unborn baby. Female patients and the female partners of male patients should avoid getting pregnant. Ribavirin is known to cause anemia (low red blood cells), which can make heart disease worse. Also, ribavirin can harm your DNA and possibly cause cancer (see medication guide for more information and warnings).
maybe you guys will all call this "old news" but it's worth revisiting, if you are considering re treating, these are just the "published" facts. anybody remember those "sleeping pills" they gave out in the 50's to pregnant mothers and said "no worries" and then the armless, legless babies atarted being born. now I'm not saying we are having babies, but there are other things more personal that could happen to our homeostasis.
Lanier
tn : hey - great to see you!
mremeet : whatever the mechansim by which riba exterts its effect, and there are 4 per that recent mutagen article (inhibition of viral RNAP, competitive inhbition of IMPDH, immunomodulary and the ever-popular HCV mutagenic effect) they would kick in at the therapeutic dose. I can see a "priming-the-pump" argument, that one doesn't reach the therapeutic dose for the first one or two weeks. However it seems you are suggesting something else entirely, that one's system somehow needs to "warm-up" to riba's effect, and as far as I know there's no support for such an effect. If such an effect existed, wouldn't it simply affect the optimal total drug duration?
Obviously nearly all of the SVRs in the world managed to reach that state even without steady-state concentrations of riba for their first couple of weeks. Nevertheless, if one is looking to extract all the benefit one can out of SOC priming the riba pump can't hurt.
All descriptions of viral kinetics emphasize the huge drop that occurs in the first phase, in the first 48-72 hours when the ifn first kick in. This wholesale slaughter of inocent virions may be even more destructive if accompanied by riba - which it usually isn't as Jim points out.
BTW, re the TVR/SOC combo strategy you brought up the other day, if it's taken more than 10 years to simply figure out riba dosages, how long do you think it'll take to figure out how to optimally combine tvr, r1626, ntz and soc?
stgeorge : you might want to take a look at aasld abstract 1310 for encouragement. Their results with daily infergen were some of the best re-tx SVR stats on relapsers I've ever seen:
1310. Retreatment of HCV Genotype 1 Relapse Patients to Peginterferon/Ribavirin Therapy with an extended Treatment Regimen of 72 weeks with Consensus Interferon/Ribavirin versus Peginterferon alpha/Ribavirin
S. Kaiser; B. Lutze; B. Sauter; L. Bissinger; C. Werner; H. Hass; M. Gregor
there should be a copy here if you scroll down a bit:
http://www.hcvadvocate.org/news/reports/AASLD_2007/Abstracts/Tuesday%20posters.htm
mremeet : whatever the mechansim by which riba exterts its effect, and there are 4 per that recent mutagen article (inhibition of viral RNAP, competitive inhbition of IMPDH, immunomodulary and the ever-popular HCV mutagenic effect) they would kick in at the therapeutic dose. I can see a "priming-the-pump" argument, that one doesn't reach the therapeutic dose for the first one or two weeks. However it seems you are suggesting something else entirely, that one's system somehow needs to "warm-up" to riba's effect, and as far as I know there's no support for such an effect. If such an effect existed, wouldn't it simply affect the optimal total drug duration?
Obviously nearly all of the SVRs in the world managed to reach that state even without steady-state concentrations of riba for their first couple of weeks. Nevertheless, if one is looking to extract all the benefit one can out of SOC priming the riba pump can't hurt.
All descriptions of viral kinetics emphasize the huge drop that occurs in the first phase, in the first 48-72 hours when the ifn first kick in. This wholesale slaughter of inocent virions may be even more destructive if accompanied by riba - which it usually isn't as Jim points out.
BTW, re the TVR/SOC combo strategy you brought up the other day, if it's taken more than 10 years to simply figure out riba dosages, how long do you think it'll take to figure out how to optimally combine tvr, r1626, ntz and soc?
stgeorge : you might want to take a look at aasld abstract 1310 for encouragement. Their results with daily infergen were some of the best re-tx SVR stats on relapsers I've ever seen:
1310. Retreatment of HCV Genotype 1 Relapse Patients to Peginterferon/Ribavirin Therapy with an extended Treatment Regimen of 72 weeks with Consensus Interferon/Ribavirin versus Peginterferon alpha/Ribavirin
S. Kaiser; B. Lutze; B. Sauter; L. Bissinger; C. Werner; H. Hass; M. Gregor
there should be a copy here if you scroll down a bit:
http://www.hcvadvocate.org/news/reports/AASLD_2007/Abstracts/Tuesday%20posters.htm
I'm all 4 re-treating, but not with whats available now. even though you think I am an idiot who attacked your hero, I really, really hope you take good care with this ribo overload. and I am sorry I hit the wrong buttons on my laptop, i have not cut my finger nails, or my dreadlocks (smile now) and my 3 teeth need brushing too. but alas I have not ribo inside my mangy body.
L Lanier
L Lanier
well it would be better if you did, at least as the ribo is changing you shole blood chemistry as it is absorbed intoyou lipo cells maybe you would be better off. what do you think will happen with that doe? do you think your erythrocytes stop being produced? they last what about 2 weeks, and tranfers lots of good and bad stuff in and out of the body via the interstial fluid. also there is the marrow and t-cells and so many other issues I can not even begin to process how it would not just put you flat out. I'll have to get my ribo bottle out, I a regular weight and in no time after starting my platelets were down to below 100, I was dosing 2x. it just seems so frightening. but I am new here maybe hundreds of you guys have dosed this "drug" in this fashion, for me, I cannot understand how. you must be in perfect health and less than 40? chronic less than 15 and low viral load, less than 1million?
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