With Sofosbuvir and Daclatasvir the world "got lucky" in that these drugs happen to be in the 30% of medicines that you can take by mouth and get into the body easily. This is called "oral bioavailability" and relates to:
A drug that dissolves well in water and crosses the gut easily is in what is called BCS class I and when taken by mouth it gets into the body fine.
MOST DRUGS ARE NOT LIKE THIS and need help. Pharmaceutical companies provide that help by using various techniques called formulation. Here is some background on this:
As you may not, Telaprevir is less soluble than marble and a great deal of work was required to convert it into a form that was bioavailable.
Looking at the other HCV drugs.
Ledipasvir will work provided it has a very small particle size and hits an acid stomach (which increases it's solubility). We know this from practical experience but it is on the borderline of the doable.
Velpatasvir is insoluble and must be formulated.
Simeprevir is insoluble, so must be Simeprevir Sodium but then there is a problem with related substance C - a toxic impurity that even the originator required an exemption on the normal limits to get the medicine to market.
Now everyone here is an adult, and it would be fair to say there's a bit of anti-pharma sentiment due to their pricing policies, but please keep in mind that there is complex science that underpins making many medications bioavailable.
Unless there is a good reason (financial or import access) using factory formulated medicine is sensible. If you plan this route choose Sofosbuvir+Daclatasvir in preference to Ledipasvir as there is more wiggle room and don't kid yourself it will just work with some of the other HCV molecules because it won't.
Just a quick reminder to people that there is more to medication that just the purity of the API. For most medications formulation plays an important role in making them "bioavailable". Bioavailable means that they can get into your body to do their work. If they don't get in you might as well be swallowing sand.
With good factory options available I suggest using those, but if you insist on using API please choose Sofosbuvir and Daclatasvir ONLY.
Ledipasvir is far less forgiving and Velpatasvir will simply not be absorbed (it is BCS class IV - insoluble and impermeable). Voxilaprevir is likely to be just as problematic as Velpatasvir so while you might be able to source it, you would do far better to wait for a generic factory formulation.
Dr Freeman, does the weight (dose) of an existing drug get reduced if the solubility rises? Is there some kind of relationship to maintain the same bioavailability? I find this new particle technology fascinating.
ALT 101 AST 71
Started Sof/Dac Jan 12, 2016
VL= <15 4 weeks in. AST/ALT normal.
VL=UNDETECTED 8 weeks in.
SVR4= Virus back. 3,300,000
Started generic Epclusa Sep. 23, 2017
4 weeks in <15 *Detected.
12 weeks in <15 *Not Detected.
16 weeks in <15 *Not Detected.
Finished 24 weeks treatment 3-17-18
SVR5 <15 Not Detected.
SVR 20 <15 Not Detected.
SVR 44 <15 Not Detected.
We need a drug to be water soluble to dissolve in the stomach.
We also need it to be fat (lipid) soluble to "float" through the gut lining and into the blood (unless there is a transporter it can hijack).
You may notice that we want both water and fat soluble.
Things that are say like salt or sugar dissolve easily in water, but ever tried to dissolve them in oil?
Similarly things like chewing gum won't dissolve in water, but will dissolve in oil (fast into orange oil gum remover for example).
Given these two almost opposite requirements only about 30% of medications have this physical characteristic. Basically they have a polar (water loving) and non polar (lipid loving) part. Technically hydrophilic (water loving) and hydrophobic (water hating, oil loving) parts.
In day to day life dish washing detergent and alcohol are two common things that have this dual nature.
BCS class I chemicals are water soluble and permeable (detergant, alcohol)
BCS class II chemicals are relatively insoluble but permeable (oily)
BSC class III chemicals are soluble but relatively impermeable (salty)
And BCS class IV chemicals a insoluble and impermeable (ie like sand or rock)