The mathematical problem with medication dosages

[rousseau]

Please let me know what's wrong with this idea.

Assume person [x] has depression and needs an exact concentration of medication in his/her system to optimally deal with their symptoms. Going over or under that amount will lead to problems.

Now consider how medication is dosed and interacts with the body:

Every pill has a half-life, and over-time, with constant daily intake a set concentration of the medication will be present in person [x]'s blood. The problem then comes with the granularity of the pill.

If the person takes 3 mg a day their subsistent concentration could be under the ideal concentration, but if they take 3.5 mg a day their subsistent concentration could be over their ideal amount. This means that pills, in their current form, are almost guaranteed to offer too high or too low of an optimal dosage.

Thoughts?

 

[beero1000]

Perfect is the enemy of good.

 

[rousseau]

Perfect is the enemy of good.

I don't know. After being in a lethargic stupor for the past two years I'm ready to fix this issue.

 

[beero1000]

Perfect is the enemy of good.

I don't know. After being in a lethargic stupor for the past two years I'm ready to fix this issue.

The dosage increments are less relevant than the dosage frequency. After all, if you're taking 3.5mg once a day, your blood concentration will vary by around 3.5mg throughout the day. Worrying about the difference between between 3mg pills and 3.5mg pills is missing the point.

What you're looking for is much more frequent, smaller doses that will allow careful determination of blood concentration. That has its own challenges, which is one reason why it's only really done in controlled situations (like an IV). I guess you could try to find an extended release pill, or something like that...

 

[ryan]

Perfect is the enemy of good.

I don't know. After being in a lethargic stupor for the past two years I'm ready to fix this issue.

I would talk to your doctor or at least the pharmacist about this. It might be more complicated than that.

 

[bilby]

This is a well understood issue in pharmacology; different medications have different half-lives, and different optimal serum concentrations.

Depending on the desired maximum and minimum serum concentration of the particular drug, you might take frequent small doses, or less frequent larger doses; And solid dose pharmaceuticals might be engineered to provide slow (aka extended, sustained or controlled) release.

The most common technique for extended release is to separate the bulk granules into three or four parts, and to spray coat each portion with a co-polymer (eg polymethacrylate) at varying thicknesses, before re-blending the portions to provide an equal distribution of each particle type in the final tablet or capsule. This effectively mimics the taking of three or four doses of instant release formulation; so that instead of taking, say, one tablet every hour, a patient can take one tablet every four hours, with the same effect on serum concentration.

Many medications with long half-lives simply do not require high-frequency or sustained doses; if 10% of the drug is excreted or metabolised per day, then a 'starter dose' of several tablets, followed by a one-per day dose of 10% of the target amount, can give a good concentration profile. Medications with short half-lives on the other hand may require slow-release formulations to reduce the frequency with which dosing must be done; nobody really wants to take a tablet every 15 minutes, for example.

Another consideration is the susceptibility of active ingredients to destruction in the low pH gastric environment, and/or harmful effects if the active ingredient is released into the gastric environment. Many drugs are 'enteric coated', for example with hydroxy propyl methyl cellulose 'Hypromellose' based compounds, that are resistant to gastric juices, but which dissolve readily in the high pH environment of the duodenum; such tablets should not be broken or crushed before swallowing, as this would render the enteric coating useless, and the label and instructions should indicate this.

 

[gmbteach]

What I have personally experienced is a dull feeling if I miss my medication. My dosage is so fine that I can tell within 12 hours if I have missed an anti-depressant or my HRT. That tells me that I am on just the right amount of medication.

I would talk to your doctor about what you are on, and other forms you could take that would give the same benefit.

 

[untermensche]

In terms of most anti-depressants no ideal maximum blood concentrations are known.

The SSRI's and NSRI's are relatively safe so blood concentrations are not measured. The effect is measured and doctors adjust doses based on patient feedback, not blood concentrations.

 

[rousseau]

I don't know. After being in a lethargic stupor for the past two years I'm ready to fix this issue.

The dosage increments are less relevant than the dosage frequency. After all, if you're taking 3.5mg once a day, your blood concentration will vary by around 3.5mg throughout the day. Worrying about the difference between between 3mg pills and 3.5mg pills is missing the point.

What you're looking for is much more frequent, smaller doses that will allow careful determination of blood concentration. That has its own challenges, which is one reason why it's only really done in controlled situations (like an IV). I guess you could try to find an extended release pill, or something like that...

Blood concentration would vary by the amount of a pill daily, but if it took a pill seven days to degrade completely, that would mean that blood concentration accrues based on seven pills, and concentration would be much higher than one pill. So if a pill degraded over the course of a week, and you did something like take 3.5 mg for 6 days, and 3.0 mg for 1 day, every week, you'd be removing .5 mg from the accrued concentration weekly.

Unfortunately, I believe where the problem would come in is if the half life is very short, and the pill actually degraded closer to one day. That would mean if you took the same action you'd actually just be removing a too significant proportion of blood concentration over the course of one day, and the rest of the days you'd still be over dosing.

So I think what I said originally still holds, and if someone was able to receive dosages that were accurate to the .1 mg, they could better manage their mood / disorder.

 

[barbos]

Please let me know what's wrong with this idea.

Assume person [x] has depression and needs an exact concentration of medication in his/her system to optimally deal with their symptoms. Going over or under that amount will lead to problems.

Now consider how medication is dosed and interacts with the body:

Every pill has a half-life, and over-time, with constant daily intake a set concentration of the medication will be present in person [x]'s blood. The problem then comes with the granularity of the pill.

If the person takes 3 mg a day their subsistent concentration could be under the ideal concentration, but if they take 3.5 mg a day their subsistent concentration could be over their ideal amount. This means that pills, in their current form, are almost guaranteed to offer too high or too low of an optimal dosage.

Thoughts?

Wow, what a profound thought!

In any case, modern fancy drugs are more complicated than having single half-life time.
You take it, then it gets in the blood stream and then body immediately starts metabolizing it while drugs acts on some receptors by attaching to it. Metabolic half-time can be short, but once it attaches to receptors it will stay there for weeks and months.
So you need to take the drug for a while before you start feeling the effect.

Correct dosage can vary wildly depending on your age, sex, state of of liver/kidneys/stomach/guts and other things. But I think there is no drugs which is as sensitive to dosage as you describe.
I saw a drug which had power of 2 dosage - 10mg, 20mg, 40mg, 80mg and so on.

 

[Loren Pechtel]

Please let me know what's wrong with this idea.

Assume person [x] has depression and needs an exact concentration of medication in his/her system to optimally deal with their symptoms. Going over or under that amount will lead to problems.

Now consider how medication is dosed and interacts with the body:

Every pill has a half-life, and over-time, with constant daily intake a set concentration of the medication will be present in person [x]'s blood. The problem then comes with the granularity of the pill.

If the person takes 3 mg a day their subsistent concentration could be under the ideal concentration, but if they take 3.5 mg a day their subsistent concentration could be over their ideal amount. This means that pills, in their current form, are almost guaranteed to offer too high or too low of an optimal dosage.

Thoughts?

In practice there is a range of acceptable concentrations. The narrower the range the more often you have to take the pill (or pseudo-take: time-release packaging), the faster the body metabolizes the drug the more often you have to take it.

Some drugs are eliminated slowly enough that you can go some time between doses. I've taken a once-a-week anti-malarial (but the same drug was used for treatment--at something like 50x the dose), many women take a once-a-week anti-bone-thinning drug. There's also an IV version of the drug that's IIRC once a year. (It's more expensive than the pill and obviously has to be in the doctor's office and you obviously a risk of infection from the IV. It's only used for people who can't comply with the requirements of the once-a-week pill or have stomach issues that contraindicate it.)