Drug absorption and therapeutic dose

[DaveC426913]

I've been wondering about absorption of oral drugs and their "therapetic" levels in the body/brain with regards to daily dosages. (I am particularly interested in SSRIs, if that makes any difference.)

(I realize there are many factors that influence this. I'd like to get an idea of the ideal situation.)

1] For a daily dose, what would the blood/brain levels of the drug look like over the course of a day? Is it a bell curve? Is it skewed (fast rise, slow decline)?

2] If the patient missed a daily dose, but took a half dose later in the day, would the curve of that half-dose be the same shape but half the height? Or would it rise at the same rate but cut off sooner?

I suppose my goal is to figure out how one might take a late-yet-smaller does so as to maintain a consistent level.

My questions could probably be simply answered by reference to some good graphs.

 

[DocToxyn]

If this is an issue of yourself or someone you know trying to determine the appropriate method to administer a drug, I would first consult the distributing pharmacologist and/or the doctor who prescribed it. Issues of metabolism are going to be very different depending on the specific drug and what it is being prescribed for. It could potentially be dangerous to modify any drug admistration scheme as set forth by the doctor/phamacist.

If you're just curious or wish to be informed before discussions with the doc, we can attempt to address the issue from a broad level here and hopefully provide you with the info you need.

As mentioned earlier drug absorption/distribution/metabolism can be a complicated question. Many variables factor into achieving and mantaining a therapeutic dose. What form the drug comes in, how you take it, how much you take, and how often you take it are some of the first things to consider. Yes in many cases the blood/tissue levels of drugs will be a bell shaped curve, but that curve is going to be very different if you are taking an ultra-fast acting barbituate anesthetic as compared to a timed-release capsule of allergy medicine.

Other things to consider are how it is metabolised, are the metabolites more or less active than the parent compound, are you taking any other drugs (or agents) that will alter the dynamics of the drug in question? There are also genetic polymorphisms between people that may make one dose of a drug therapeutic for them and not effective for another individual. In this case the dose may have to be "tailored" for that particular person under the supervision of their doctor. I think this can be rather common in the use of antidepressants like you mention.

As far as missing a dose and taking half a dose later in the day, this may be a sound strategy. Many drugs work at some therapeutic level like you mention, but that level may be a rather broad range of concentrations and if you have achieved that level by prior doses the actual concentration may indeed go down because of the missed dose, but the effective dose is still in the desired range. However this ay not be the case for all drugs and therefore heed the warning above and talk to the professionals.


Here are some links I found that may provide some more information if I haven't gotten to what you were looking for.
http://www.aegis.com/pubs/beta/1997/BE970907.htm"

http://www.biopsychiatry.com/metabolism.htm"

You can also try your own searches using terms like drug half life, therpeutic dose, effective dose, metabolism, drug kinetics or disposition...

 

[DaveC426913]

Yes, this is for me, and really, I'm just curious. I appreciate the caution, and will exercise due diligence.

As with all meds, they tell you to take the dose as soon as you remember. But taking a whole dose when the next dose will be in less than 12 hours will tend to over-dose somewhat, though not harmfully - it is a perfectly fine rule-of-thumb.

Also, I recognize there are many factors that come into play, I'm really considering the "all other factors being equal" scenario here.

So, what I've been trying to reconcile is:

1] These meds take a long time (days/weeks) to build up a therapeutic dose. This would suggest that each subequent dose is leaving a little behind in the body. That suggests the curve of a single dose is not truly a bell curve - it will rise normally, but drop off asymptotically. After enough time, any single dose (see BLUE curves on attached graph) will only be a fraction of the total dosage (see LIGHT blue line ) in the system. Is this generally correct?

2] A half-dose. What is the curve of a half-dose compared to a whole dose? Does it:
- RISE at the SAME rate as a full dose yet level off EARLIER (see BOTTOM PURPLE line).
- rise at a SLOWER rate than a full dose? (see BOTTOM MAGENTA line).
(The Full dose and No dose lines are merely there for reference.)

 

[DaveC426913]

Yes, actually, reading your references helps too.

The curve is actually logarithmic - dropping by half with each passing unit time. In the case of my drug, its half life is 21-26 hours. So my graph is qualitatively accurate.