TOPIC:

I found a very detailed EMA research document (which I have linked to somewhere on this forum), which makes clear that doses for these meds should, strictly, be patient weight-related. But, because of the impractical nature of actioning this, the pharma co's came up with a happy medium 'one size fits all' pill. Dr Freeman has also posted here on this, and his views on structuring dosages for more 'extreme' body weights would be useful. It might be that lower-weight patients could start on the standard dose, but adjust their dosage (using a pill splitter) if the side-effects were extreme.

IThank-you Alsdad - I shall go In search of your / Dr F's link! When you think that I am 2 stone less than half your weight for example, it seems kind of crazy to me that we would have the same dose!

It would still be interesting for me to know people's rough build , eg light, medium, heavy build I know frame and body mass are considered for example, when deciphering the 'ideal' weight for your size /height.

Everything about me is small,; bones, height , frame, shoe size but weight has severely dropped with muscle-loss now too. I eat loads, it just doesn't stay ! Everything seems geared towards losing weight, it's hard to find much on gaining weight. I want to gain some weight before starting treatment, have been trying, but over a concerted effort for over a year, I have managed to gain 1 - 2 kgs. I want to gain weight for me, as a person, not just for treatment, although I just know it would be helpful. I sometimes worry about absorption of Meds too, as I don't seem to absorb anything much at all!

Would like to add, this will NOT deter me from treating, but may help in organising time to start with work/life responsibilities etc

This is a link to the Sovaldi PDF document:



www.google.co.uk/url?sa=t&rct=j&q=&esrc=...7eMAuxXnkkcA&cad=rja

And here are the links to PDF documents for Daklinza and Harvoni:



www.google.co.uk/url?sa=t&rct=j&q=&esrc=...841590,d.bGQ&cad=rja

www.google.co.uk/url?sa=t&rct=j&q=&esrc=...841590,d.bGQ&cad=rja

First of please understand that all the trial data you read is typically based on a "one size fits all" dose. Unless there is a good side effect reason to vary....don't vary, take the recommended dose.

Now on to theory.

For every drug there is what is known as a therapeutic index. Making the rash assumption that everyone knows alcohol we see that the theory "if a little is good, more must be better" does not necessarily hold.

Alcohol is a drug and we see three general things:

The first has the technical name "Therapeutic Index". With alcohol this looks like:

• Low dose - not much happens
• Medium dose - happy
• High dose - punchy, miserable or beer goggles issues
• Overdose - steering the toilet or lying in the gutter unconcious

We also see the second thing called "Tolerance"

• As a teenager a couple of drinks might have got you to medium dose happy
• Push that for a while consistently and your dose requirement might increase to a bottle of wine
• Continue long enough and the bottle will need to be Scotch

We also see the third thing, often disguised by tolerance:

• Small people can't drink as much and get drunk on less

So how does this relate to real drugs, as in medications?

So given a promising new drug the first task is to work out the therapeutic index.

The phase 1 study of Sofosbuvir might for example of experimented with doses like (for 75 kg average body weight)

• 0.66 mg/kg 50 mg - does not work
• 1.33 mg/kg 100 mg - just works
• 2.66 mg/kg 200 mg - really works
• 5.33 mg/kg 400 mg - really works
• 10.66 mg/kg 800 mg - really works
• 21.33 mg/kg 1600 mg - really works but getting sides
• 42.6 mg/kg 3200 mg - really works unacceptable sides

So on that basis we would decide 200-800mg looks good.

400 mg is best because if that works in a 75 kg person (at 5.33 mg/kg) then a 150 kg person would get 2.66 mg/kg (works) and a 37.5 kg person would get 10.66 mg/kg (works). When the therapeutic index is wide a one dose fits all dose is convenient for manufacturers who then only have to make, and pay for regulatory approval for one dose.

Tolerance to a medication develops for a number of reasons but to keep it simple we will just consider metabolism. You liver has some general purpose garbage collection enzymes (Cytochrome P450). CYP3A4 is one example and helps remove daclatasvir from your system. Our bodies are reasonably clever and run a kind of "just in time" metabolism increasing the levels of garbage collection enzymes in response to need.

By way of example a 50 kg jockey was taking Sof/Dac and still getting sides 2 weeks in. Of his own volition he halved the dose of Dac and the sides went away. At 2/3 dose they came back mildly and at 3/4 dose more. Worried about not taking the full dose he gradually got back to the full 60 mg dose over time - being able to do this probably represented the development of tolerance.

A very interesting and pertinent question.


Like you, LondonGirl, though not particularly short I am quite a lightweight and find it difficult to put any mass on. Having had a run if hep C-unrelated health issues this year has seen me spending much of the time since March lying down, which of course hasn't helped.


Its not only weight which is a factor in dosage, but also age and the effect of a decreased metabolism. My 92 yo mother cannot tolerate even the smallest dosage of blood pressure meds sometimes and must try and cut the pills otherwise it falls to disturbingly low levels.

Agreed Zhuk, I had an extremely bad reaction to taking one Ibuprofen for lower back pain at night, it made me extremely ill, first and last time I'll take that poison! We are all different, one size fits all approach is, 'interesting' !

Yes, very interesting post from Dr F above.