Hep C Discussion Forum

mallani · Guru

RE: Action of Ribavirin

wmlj1960 · Moderator

I've been eating a very low fat diet lately with the idea that fat just provides a barrier to the medicine laced bloods ability to gain access to the virus to kill it. If a fatty meal increases bioavailability then is my low fat diet a mistake?

I understand about us cirrhotics, especially late stage, needing longer exposure time in order to reach underperfused areas from another one of your post. That's partly the reason why I've been doing a lean diet - so the plasma won't have to penetrate through fat deposits in addition to penetrating the hard liver scar tissue.

Gee I've got a lot to learn about this disease.

Thanks again Malcolm.

mallani · Guru

Hi Mike,

Ribavirin is absorbed from the small intestine into the blood stream using various transporters. The most important one is called N1 sodium-dependent nucleoside transporter. There are others, and the types and amounts vary from person to person. The Riba is then free in plasma, and is not bound to any of the plasma proteins. Absorption is rapid (~2 hours) and peak concentration is reached quickly. Food increases the bioavailability, and a fatty meal increases it even more. There's a simple test to measure the plasma concentration. Antacids and foods high in purine ( meat, fish) limit the bioavailability.

Riba is useless as it is- it needs to enter cells and be converted to a phosphorylated form. Again, it needs a transporter to enter cells. We end up with ribavirin monophosphate, diphosphate and triphosphate. The triphosphate form is actually a NS-5B blocker (bit like Sovaldi) and this is one of Riba's antiviral actions. Red blood cells don't have any enzymes to remove the phosphate, so the Riba triphosphate accummulates, eventually causing cell death. This haemolysis eventually leads to anaemia. Researchers have measured the concentration of Riba triphosphate in RBC's. This has been used to predict the degree of anaemia to be expected. It was found that the plasma level does not exactly correspond to the expected triphosphate levels- meaning this varies from person to person.

I'm struggling here- trying to keep it simple.

Research using the old SOC, found patients who could reach a Riba plasma concentration of > 2 mg/L had a 86% chance of SVR compared to only 27% of patients who reached a Riba plasma concentration of <2 mg/L. This is probably not as relevant when Riba is used with the new DAA's.

In short, we take our Riba as prescribed ( weight-based) and hope we get adequate plasma levels. Then we hope it can enter cells like hepatocytes and the various phosphate forms do their jobs. We hope the concentrated triphosphate in RBC's doesn't cause severe anaemia. In cirrhotics, we need to take it for long enough so that it can reach all the underperfused areas of fibrosis. It's a bit of a lottery. Cheers.

Matt Chris · Guru

mallani wrote:
Patients vary enormously in their ability to absorb Riba, and there is also variation in the concentration in red blood cells. For the last 15 years, patients have had their plasma concentration measured, and this has been compared to SVR rates,

Absorbing in the bloodstream I believe is relative to the plasma concentration, but how much the liver is exposed to the Ribavirin via bloodflow is something that is likely diminished with cirrhosis, but how much less I do not know.

matt

-- Edited by Matt Chris on Thursday 7th of August 2014 05:07:39 AM

Isiscat2011 · Guru

Good question, Mike. I was just wondering the same thing myself. I am constantly amazed at how much we can learn here. Malcolm is just going to have to stay until everyone is SVR.

wmlj1960 · Moderator

mallani wrote:
Patients vary enormously in their ability to absorb Riba,

Is it known what the reason for this is? Do you mean absorb into the liver itself or into the bloodstream? If the liver itself, wouldn't stage of fibrosis be a major factor determining absorption ability?

Thanks for the post Malcolm!

Huey · Guru

I pushed the LIKE button :)

/We are all in this together Keep your stick on the ice,Red Green Show;

mallani · Guru

Hi all,

Ribavirin will still be around for a while, and it's an interesting drug.

It has a multi-pronged action on the HCV, and this is still poorly understood. The correct dosage has been debated for years, but most agree weight-based Riba is the way to go. That means an average male will have 1,200 mg/day, and 1000 for a female. The dose is taken twice daily with food. It takes about 4 weeks to obtain a steady-state plasma concentration, and this remains constant during treatment due to the long half life.

Patients vary enormously in their ability to absorb Riba, and there is also variation in the concentration in red blood cells. For the last 15 years, patients have had their plasma concentration measured, and this has been compared to SVR rates, and the degree of anaemia. It is now pretty well accepted that a concentration of between 2 and 2.5 mg/L is optimal. When concentration rises above this level, the anaemia becomes more severe. Below this level, the SVR rate declines. Obviously, anaemia is one of the main problems for patients. Dose reduction and drugs like procrit can be used. The danger with dose reduction is that the plasma concentration may fall below the desired level. Some Hepatologists actually monitor the plasma levels, but most don't seem to bother. The degree of anaemia is taken as a rough guide to Riba effectiveness. Usually a drop of ~3 gm/L in Hb is taken to be good enough. Some patients are more likely to develop more severe anaemia ( less than 10). These are patients older than 50, females, those with Geno 1 and those taking Interferon as well. The protease inhibitors also increase the degree of anaemia. For patients taking Riba, there's a good chance that dose reduction will be discussed at some stage. Why not ask your doctor for a blood test to check the Riba concentration? It's a valid question. Cheers.

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