Posted by chemist on May 16, 2004, at 23:14:38
In reply to Chemist...question, posted by chess on May 16, 2004, at 21:37:06
> Chemist
>
> What's the difference between the half-life of a drug and its duration of action?
>
> Like klonopin for example. I've read that its half-life is 18-50 hours, but that its duration of action is 8-12 hours.
>
> Is that why you have to take klonopin more than once a day even though it has a half-life of 18-50 hours, because even though it lasts in the body for 18-50 hours it is only working therapeutically for the first 8-12 hours?hi chess....half-life of elimination is the time at which one-half of the parent compound can be found to reside in your system: more accurately, it is determined (usually) via excretion of drug in urine. the duration of action has to do with a measure called (in general) bioavailability. when you take a dose of klonopin, the time to what is called maximum area under (the) plasma concentration curve (AUC) [t__{max} AUC] is what we want to talk about. since the drug is being metabolized, excreted, and, as in the case of klonopin, highly plasma-bound, we can expect that klonopin will partition into fatty tissue in your body (this comes into play later) and that the onset of action - and duration - is determined by the ``balance'' of bioavailability vs. elimination. these factors - and others, but these are the major ones (in my experience) that address your question. so: you dose. the dose gose to your gut, where some degradation of the parent occurs. the kidneys excrete parent + metabolites and this is a (usually) first-order process, i.e., the change in concentration of the parent is linear in time or, at best, a pseudo-first-order kinetic process). now, it turns out that the plasma binding is not the only way to go, because much of the parent (and metabolites) have partitioned into your fatty tissue (like likes like, i.e., oil and oil are miscible, oil and water are only slightly so). so the AUC business must be taken into account with plasma binding, which is how the parent gets to your active site. turns out that the higher plasma binding, the lower the potential for unchanged parent to reach the receptor. but this is an issue iff (not a typo: if and only if) the plasma protein interacts with the drug, thus making the unbound fraction more potent due to retention of potency. so: the elimination includes perfusion from the fatty tissues, and this is what make withdrawl, well, withdrawl. it is also a boost if you can perfuse the fatty-bound drug into your system, e.g., with a vasodilator. the onset of action is how quickly the drug starts doing it's thing; and the duration of action is a balancing act between how much parent is partitioned into adipose, plasma, and is being eliminated. please let me know if this helps or hinders....all the best, chemist
poster:chemist
thread:347588
URL: http://www.dr-bob.org/babble/20040515/msgs/347622.html