185

This was originally published here, in French (link).
We provide this translation for your convenience. Practical aspects may differ where you live.



Isobolograms and the ineptitude of the single dose

By Charles-Edouard!

Isobologram: oral vs. injected dose

For those who practice ICCARRE-Premium (1/7 or better) the question of dose is subsidiary. With injectables, for the others, the question of the dose comes back, with an extreme acuteness: overdose guaranteed for 95% (or more) of the patients.

One of the arguments in favor of unnecessary (or even deleterious) overdosing is that many patients take their daily medication incorrectly. This is probably more pronounced in countries where supply is variable or even random (e.g. Maghreb). Okay, okay... Let's go for a 'regulatory' argument but what about the metronome patient? Does she have to dose every day, because Algerian women or others have problems to get supplies? Should she fill herself up daily with the pretext that the homeless desocialized, abandoned, are more and more numerous, and have real problems?

Another argument can be proposed: the variable bioavailability: it is, for example, notably problematic for Raltegravir for which Merck will have made the galenic 3 times!(At the end, they went as high as ... 1200 mg/d !!! And it was authorized! - To my knowledge, nobody takes it - ...): we inflate a little, because well... You never know... Especially since we don't want to know... With injectables, this argument is not valid anymore!

A single dose without taking synergies into account

Leibowitch kept coming back to the famous synergies, without any real further explanation. It's not that complicated. Take an antiviral A and an antiviral B, when you use both you can have an antagonistic effect (A + B is less than the expected sum of the effects), a purely additive effect (A + B gives the expected sum of the effects) or a synergistic effect (A + B does better than expected). Apart from any pharmacokinetic consideration...

Ritonavir improves intake by a known pharmacokinetic effect of slowing down hepatic metabolism: it is not a synergistic effect.

When La Scola (Raoult team) shows in vitro that HCQ + AT works better than the simple sum of the effects, it is synergy: there is no pharmacokinetic role (e.g. metabolism by the liver) in a test tube... On the other hand, there is no synergistic interest to put 2 NNRTI (ex. NVP, EFV, RPV) in a combo...

However, if we look carefully, the usual dose of a molecule is a unique value, which NEVER takes into account what we put with it.(there is at least one recent exception: do you see it?...).

What is an ISOBOLOGRAM?

Ah well... It's easy to understand!... It's like Isotherms or Isobars: we draw the curve of same efficiency by varying the dose of each component. The diagonal is the neutral curve: on it the effects of the products are added, simply. As for Dalton's law for gases: the total pressure of a gas mixture is equal to the sum of the partial pressures. One mixes, it adds, no more no less. If the curve is in the SYNERGETIC range, less A and less B are needed to obtain the added effect of A and B. On the contrary the curve can be in the ANTAGONIST (= ANTI-SYNERGETIC) area, in this case you need more A and B when mixing A and B to obtain the same combined effect.

A now famous example of SYNERGY is the addition of HCQ to Azithromycin, at usual doses, which is much more effective in neutralizing SARS-Cov2 than HCQ or AT alone: this is why the idea defended by G. Pialloux was stupid, i.e. to test HCQ alone! The guys are czar infectious diseases specialists, but SYNERGY ?? They don't get it... Yet it is a great classic for... Tuberculosis or malaria... Of course, this is done in vitro. In real life, you might have to test a bit, but at least it's a guide.

Efavirenz-Entricitabine (Atripla ™) isobologram:

In Atripla ™ we find the STANDART dose of Efavirenz (600 mg) plus the STANDART dose of Entricitabine plus the STANDART dose of Tenofovir. I give you a first Isobologram, where you can clearly understand the ineptitude of the thing!

We have no scruples to say that it is completely stupid! Since the ENCORE1 trial has proven that 400 mg is as good (or even better...) than 600 mg. We know that! Sponsored by Bill Gates... The Morlat report endorses this alternative... The 400 mg combination drug exists (Mylan). But... But... It is not marketed in France.

Look for the mistake! We'll see all this next time...

Weekly intake, 1/15 and treatment obligation

January 24th is my freedom day! Phew, it's over... The 1/15 means 24 doses a year, no more! It's an important day. Well...

Instead of pissing them off, we should give a medal to all those who have gone through 2 years of pandemic without getting sick even once!

Everyone will have understood what is coming next in terms of public health and that injectables, QR codes and other technological prowess will promote.

I keep well far away and the obligations suffered in France and elsewhere amaze me. And I find it very sad...

In the news

- I had quoted Pr. Fenton's intriguing post: The delay of 2 (or even 3) weeks between the injection and the validation of vaccination would not distort too much the efficiency if it wasn't for the ADE. Canadian statistics (Alberta): 50% of Covid cases occur within 2 weeks of the 'protective' injection. Not only are these people not counted as vaccinated, but they are counted as non-vaccinated, which they are not... Kiss Cool effect guaranteed on the efficacy ratio. We reduce the denominator, we increase the number and there you go! 95% efficiency on the counter... Except that the counter is a TV commercial...

- Along the same vein: DRESS (a French governement statistics body). Not knowing how to extract the vaccination status of all, it allocates the unknown cases between vaccinated and non-vaccinated according to a fanciful distribution key but favorable to the vaccine: vaccinated people are counted as non-vaccinated: and tada! We should say: not knowing, we don't count them, but here, we count them in the category that 'suits' our narrative best. Except that it is obvious and it looks ugly!

- Marco Nius makes an amazing simulation. On a small number of people, a marginal error in classification is enough to increase the relative risk from 1 to ... 5!

Feel free to comment, like, share and use

Turn off the TV and don't be fooled by the Parisian venality