Posted by chess on May 18, 2004, at 14:39:19
In reply to Re: Chemist...questionChemist » chess, posted by chemist on May 18, 2004, at 14:15:30
> well, thank you...the ~ 0.5 mg klonopin still in you at midnight will be hitting your GABA receptor BUT not with the heft of the plasma-bound fraction
-----does that mean that fewer gaba receptors are being hit as time goes by, or does that mean that klonopin is still hitting the same amount of gaba receptors but just not as powerfully as before?
, and will include active metabolites of klonopin more than the parent. the plasma-bound fraction is more accessible in that it crosses the blood/brain barrier,
-----does the blood-brain barrier allow hydrophilic meds or lipophilic meds to pass through it?
and the hydrophobicity of klonopin (relatively low solubility in water) means it ``prefers'' to partition into something other than water
-----does that mean that klonopin is lipophilic?
, such as a protein matrix that does contain chemical groups that in turn make the whole mess soluble and thus transport is enhanced. the non-plasma-bound fraction is the stuff that partitions into your fatty tissues, and it's harder to remove the drug from these depositories than from the adsorbed/incorporated goods in your serum.....hope this helps, all the best, chemist
> > chemist,
> > before asking more questions, let me say THANK YOU!, and also say that you are more than helpful!
> > question ... if I take 1mg klonopin at 6AM, and around midnight there is around .5mg still in me, is that .5mg still affecting gaba receptors in my brain? Or is that .5mg at midnight of inert quality and having no affect on my brain gaba receptors?
> > question ... when you said “12 hours after taking klonopin there is still klonopin in your body, it's just less-accessible than the plasma-bound (and mostly used up by now) fraction”, what do you mean by "less-accessible"?
> > >>
> > >>chemist, I think I got it, but please correct me if I'm wrong with the following example ...
> > > > accepting 8 hours as being the duration of action of klonopin, and 18 hours being the half-life of klonopin, is the following example correct?:
> > > > 6AM: I take a 1mg tab of Klonopin
> > > > 8AM-2PM : there is 1mg in my blood
> > > > 2PM: amount in my blood starts to fall below 1mg
> > > > 12midnight: there is .5mg in my blood
> > > *** almost. given an 85% plasma-bound concentration, at midnight, you are looking more likely at 0.425 mg plasma-bound....but this is splitting hairs, you are on the right track! all the best, and please let me know if this helps or if there are data that indicate otherwise....all the best, chemist***
> > > > > > chemist,
> > > > > > so then what you're saying is that klonopin lasts 18-50 hours in the body BUT it is only bioavailable to get into the brain and work therapeutically for only 8-12 hours BECAUSE after 12 hours it begins to bind to plasma in the body and thus is no longer bioavailable to get into the brain?
> > > > > **** the deal is: if you were to measure for the presence of klonopin in your body - and i mean all throughout your body - after a dose, then somewhere beteen 18 and 50 hours, the number (let's say you took 1 mg) would be 0.5 mg. the time between when you took the 1 mg and the peak amount found in your blood is 2 hours. so, for the next 6 to 10 hours, there is enough drug in your system to do what it needs to do to the receptor it targets, which is becoming desensitized over time. now, there is still klonopin in your body. the plasma-bound fraction results immediately after ingestion and some hepatic metabolism, and then it rides along into your brain. but now we are talking 12 hours later, and frankly, there isn't much of the `mobile'' drug piggybacking on proteins in your blood to keep the anxiolytic effect at full-strength. but there is still klonopin in your body, it's just less-accessible than the plasma-bound (and mostly used up by now) fraction. but this is why you take another dose 12 hours later, to boost it back up. if you stop taking klonopin (slowly!), then after a week or so your body would probably be quite literally clear of any and all traces of the drug. but 2 or 3 days into your taper, you could still find it lingering around in fatty tissues, maybe some in the blood, etc......all the best, chemist
> > > > > > > > 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
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poster:chess
thread:347588
URL: http://www.dr-bob.org/babble/20040515/msgs/348238.html