Posted by Miguel (184.108.40.206) on February 13, 2000 at 13:06:17:
In Reply to: Thanks, but posted by Todd on February 13, 2000 at 07:39:38:
I basically agree with what you described as the effect of the drug being the same. Clearly, the drug hits the same receptors, regardless of which way is making its way into the blood stream (unless, of course, a metabolite, perhaps active, may end up making its way into the blood stream from the gut, which is kwon to happens, i.e.: Zantac as an example - that is why pharmaceutical co's. patent the parent drug, isomers and metabolites when launching a drug into the market). What I am trying to explain, and without going into way to many formulas that may not make much sense, as well as not having the benfit of access to the specific metabolism of Imitrex in its several dosage forms, is that Imitrex is proven effective in all dosage forms available in the market. The way I understood your question was: Why is Imitrex less effective in one dosage form than in others (i.m./sub-q, v. gabage, or intra-nasal, and without one being effective v. totally not effective in the other forms)? Correct?
If my understanding of the question was correct, the answer I posted may help you understand. All forms marketed are effective. What I am trying to explain (and without postulating a polarized answer of effective v. not effective at all) is that what you are looking at is different pathways by which the drug gains entry into the bloodstream, some more direct than others, some perhaps quicker than others. If I understand correctly, you mention that aparently there is a bit more of leeway when noticing the "shadow" as to how much time you have before taking the drug when comparing gabage v. intra-nasal or i.m. dosage forms. Via gabage, one has an entire gut system to interfere with the absorption of the drug, which is not the case when taken via i.m. or i.n. Therefore, if metabolism rules apply in general form to Imitrex (a big if without the data) the effect of Imitrex should give you more leeway as to dosing yourself via i.m. injection than via the p.o. or i.n. routes.
The ther part of your question may also be explained at the physio-pharmacological level - receptor affinity for drug v. causing agent, or messanger affinity if the path involves second messangers as the key mode of action of the drug. This affinity is dependant on several types of relationships between receptor, if a specific or variety of receptors are involved, and the causing agent v. Imitrex. The affinity depends on the intrinsic chemical characterisitics of the drug v. the causing agent/messanger. How tightly does the causing agent bind to the receptor v. the drug? How long does the receptor-causing agent relationship last? What type of relationship is it? irreversible? reversible? How much time, if the later is true, does it take for the receptor and causing agent to reach equilibrium state with the ensuing receptor-causing agent disociation to take place? How does that compare to the data for the same relationship between drug and receptor? If the raletionship between receptor site and cuasing agent is irreversible, is Imitrex acting through a secondary pathway, i.e.: as in disrupting second messanger signals from the receptor?
Metabolically speaking, and asuming that everything is the same relationship-wise for drug and causing agent ( a hughe if without the data), and that the relationship between receptor and causing agent is reversible (another hughe if and specualtion without the specific data), assumng that the binding between receptor and causing agent and drug is not competitive (another even hugher if without the data - sh*t...I am way out on teeny-weeny end of the scienific long branch right now!!! roflmao!!!), assuming that both, drug and causing agent, are working on exactly the same pahtway or receptors (another one! lol), the drug get there, the effective site after the causing agent. This is evidenced by the time it would take for the drug to get absorbed into the blood stream, an occurance that is hardly instantaneous unless it is being administered i.v., which is not the case. Under those conditions and depending on the [Drug]max, and t1/2 of the drug in plasma, you are looking at a fight then - between drug and causing agent. It is indeed a fight for the receptor (if a receptor is involved). Depending on who wins the fact, you have an effect, or you may not.
Again, by all of the above, I am not advocating that one form of dosage is effective and the other is not at all, but re-statng that there will be differences between the two at the metabolic, and physio-pharmacoligical levels.
However, if the above does not clarify it, or even address the question, would you be kind enough to either post the question again, or e-mail?
These are rather
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