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Biotech / Medical : Sepracor-Looks very promising -- Ignore unavailable to you. Want to Upgrade?

To: jayhawk969 who wrote (4598)	10/20/2000 2:09:17 PM
From: tommysdad	Read Replies (4) \| Respond to of 10280

<<Slightly off topic:>> Actually, I don't think it off topic at all. I think it's pretty important to help analyze SEPR's "racemic switches". The key phrase you pasted is: <<There are some reactions referred to enantioselective reactions >> Racemic drugs, such as Prozac, are not prepared using any enantioselective techniques. That's what I meant by "physically impossible". Thus, they are truly racemic (e.g., 50:50 mixture of enantiomers). I am not aware of any marketed drugs that are sold as non-racemic mixtures of enantiomers. So, in the case of a racemic switch, SEPR is competing with a 50:50 mixture. Thus, at an equivalent (by weight) dose, they are actually dosing twice the amount of the "active" or "preferred" enantiomer. That's important to keep in mind. Someone suggested that one enantiomer much have caused QT effects while the other counteracted it. Possible, but not the only possibility. Another possibility is that the S-enantiomer induced certain P450 enzymes that were involved in the metabolism of R. Thus, with no S around, less R was metabolized by these enzymes. What this means is that at an "equivalent" dose, the patients would actually be exposed to more, perhaps much more, R drug, presumably for a longer period of time. (I would hope that SEPR/LLY looked into this possibility pre-clincally.) Yet another possibility is that the S isomer competes for absorption versus the R. Dose only the R, more gets in. Same net effect as above. Many other scenarios could be envisioned. The take home message is that, yes, there is 1 unit of the "right" enantiomer in every 2 units of racemic drug. But that 1 unit may not behave the same way in a human body if dosed in the absence of its "evil twin". Personally, I think Lilly just bailed because they don't have any guts.