Calum
Hi Calum,
I can only answer from the perspective of someone who calculated
doses of alcohol for experimental subjects many years ago. It was not
possible to apply a linear function across the range due to a number
of factors. One is that BAC, which was the target value, is dependent
upon the proportion of the weight that represents the water
compartment of the body. This varies with both weight (heavier people
typically have a higher proportion of fat) and sex (women also tend
to
have slightly more fat). The real monkey wrench in the works was
absorption rate, which often made nonsense of my calculations. This
may not be as important in therapeutic drugs, for we were aiming at a
specified BAC at a certain time after dosing rather than an average
level.
All those things affect therapeutic dosing.
I may have oversimplified what we are trying to achieve to avoid
getting bogged down in the detail of what we are trying to achieve and
provide something people might be able to relate to.
However, we can assume that they are already sorted out, so we know the
theoretically know what the 'correct' dose is for a patient. The hard
bit is unless you want to give everyone liquid so you can measure any
dose possible you have to have a dose that is a multiple of something
(Amoxicillin doses in adults are multiples of 250 because thats the size
of the capsule).
What we are trying to do is determine the most appropriate number to
make the capsules. (Our dosing is more complex but lets stick to
something simple. I can safely assure you that vritually no-one
actually needs 250 or 500mg as a dose of amoxicillin... ...thats just a
dose to get them into a therapeutic window, and I'm 99% certain 250 and
500 are used coz they are round numbers. if 337.5 more reliably got
everyone in the window without kicking anyone out the window that'd be a
better dose to use! So... what I'm looking to do is model the
'theoretical dose required' (which we know) and the dose delivered using
several starting points to get the 'best fit'. We know they need to be
within 7% of each other, but if one starting point can get 85% of doses
within 5% we think that might be better than one that only gets 50%
within 5%.
However, I suspect that many therapeutic drugs have a different
dose by weight for children (we weren't dosing children) and choosing
a starting point at the bottom of the range would almost certainly
introduce a systematic error. My intuition would be to anchor the
dosage rate in the middle of the scale and then extrapolate in both
directions (adults only, of course).
We are actually using a starting point that may be middle and going up
and down if need be.
I think what we may want to do is run a loop through each weight (in
1kg increments) and calculate their theoretical dose, and the dose for
each possible starting point (there are certain contraints on that
already so there may only be 20 possible start points), then we
calculate the % variance for each dose to theoretical dose and calculate
the Area Under & Above (some will be negative) the curve and the one
that has the lowest AUC is then the one that most "precisely" will dose
the patient...?
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