George J, I was a bit delayed due to Thanksgiving travel and festivities but here we go. I hope the wait wasnt too long.
Quite an interesting response from you I must say. Basically, you were unable to demonstrate any significant level of conceptual grasp over things that you claimed to be an expert on. Instead you prefer to pull out
stray issues where you feel you have a little bit of breathing room. But, I will play along just to stick it in for one last time. Lets have a look at them and deal with them appropriately. And about Oseltamivir's MOA,maybe it is specious and maybe it isnt - how would you know any way? You keep on doing what you do best - being duplicitous.
1) Utility of SC dosing over oral dosing for a second line ARV (you
were more interested in explaining the MOA to me when I didnt ask you for it)
Fusion inhibitors were brought into this argument by you. I discussed Fuzeon because it is a great line of treatment against current variants of drug-resistant HIV strains. I NEVER argued that it was a first line ARV. I also indicated clearly that it was unsuitable for India and Africa primarily because of COSTS (>$15K/year/patient). The argument about oral vs. subcutaneous dosing is secondary because:
(i) Even if Fuzeon was an oral drug, its price would be prohibitive for widescale utility in India and Africa.
(ii) In contrast, if Fuzeon was as cheap as generic ARVs, SC dosing can be dealt with in a manner similar to SC dosing of insulin. Despite the relative complicated administration, a very cheap version of Fuzion could be rationed out to educated/skilled workers who are infected with drug-resistant HIV (doctors, nurses, some social workers, policemen, engineers etc.) This would help sustain the health care infrastructure and the economy in AIDS-infested regions of Arfrica. In short, it could be rationed out selectively. The logic is simple and if you still dont get it, in addition to being cenceptually bankrupt, you need to worry about your neurofunctional deficits that may be beyond salvage.
Your point #2:
2) Your vast knowledge about what BMGF do in India. (they pay for drugs in India? right)
This is what I wrote and you can check it yourself.Those who do get it for free need to thank BMGF, I guess.
Note the word "guess", which clearly telegraphs an element of uncertainty. You indicated that wasnt the case and I didnt challenge you on that. I realized I guessed wrong....after all, it was a guess.
Your point #3:
3) Your wonderfully uneducated views about the demographics of HIV and DM patients in India/Africa and hence the ultrasimplistic view about the ease of parentral self administration
I brought up diabetes because you were making a big deal about subcutaneous dosing. Insulin is injected subcutaneously by millions of Indians and its not a big deal. Even small children who have type I can be taught to self-administer SC injections. The primary issue with Fuzeon is cost and not the SC dosing and certainly not sterile water (as you claimed first (remember the bisleri comment
). And what uneducated views did I express about demographics of HIV and DM in india and africa...pull out some quotes so that I know what you are talking about.
your point #4:
4) And finally thiazolidinedione (TZD): (you were trying to justify the SAR for PPARg when I didnt ask you for it, and you got TZD).
What do you mean by "SAR for PPARg"? Structure-activity relationship (SAR) studies are carried out on small molecules and not on proteins - but anyway, coming from you thats nothing new (conceptually vacuous, just flashy abbreviations
). And no, I wasnt justifying anything, I was elaborating on how Dr Reddys came up with the drug. Your explanation about how they came up with it was superficial (and lets face it, you didnt really have a clue about PPARg agonists anyway - as was aptly demonstrated previously).
And before you think of retorting that I am trying to draw this topic BACK
to the AIDS, Indian Pharm and R&D, let me remind you its was thanks to your incorrect notions (GSK reducing costs right!) that you drew me into this discussion.
This is what I wrote about GSK: companies like GSK for example (who actually did the research behind
ARVs) gave a voluntary license to South African generics firm Aspen to produce AZT, 3TC and Combivir without charge. In return, Aspen had to
promise 30% of their revenue to NGOs fighting AIDS in Africa.
There may be more to the picture, but the statement is accurate.
So its in my right to expect you to respond to those issue rather than argue ion channels, ligands and other stuff that are of NO Relevance to this discussion.
That and more is of relevance because you are masquerading yourself as someone who understands the science behind drug discovery by making assertive challenges such as:
Now we know that you are the one full of BS and VERRRRRY BAD with even the most basic aspects of preclinical and pre-formulation stages of drug discovery. If you dont understand things, dont go around making an ass out of yourself by making such statements.
Thats all BS. Indians are VERRRRRY good at preclinical and pre-formulation stages. They are very good in candidate screening, tox etc.
Furthermore and in a very similar manner, you also asserted that there was "no paucity in the small mol infrastructure in Indian companies"
. You moron, how the hell would you know? You cant even recognize the most basic instrumentation in a research laboratory by your own admission. For all I know, you could be convinced that an undergrad lab in a community college has no paucity of small mol. infrastructure either. Difference between bisleri and sterile water, huh?