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I encountered a mathematically intriguing conundrum, in that it's related to medicine but is centered around mathematics.

Suppose drug A has a half-life in the body of 30 hours. The patient takes 40mg once per day. How long is it then until the patient then reaches steady-state dosage in the body (within some tolerance interval)?

The answer should be about one week, but I'm trying to understand the math behind "why".

askquestions4
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  • Define "steady-state dosage". – Adam Rubinson Oct 10 '22 at 18:28
  • Non-changing, constant. This wouldn't exactly "physically" happen given the differential mechanics of a half-life, the actual physical amount would be fluctuating, but that's why I said "within some tolerance interval". – askquestions4 Oct 10 '22 at 18:29
  • Hint: if there are $x$ milligrams of drug A in the patient’s body at the end of some day, how much drug A is there in the patient’s body at the end of the next day? – Aphelli Oct 10 '22 at 18:30
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    @askquestions4: The answer depends on the tolerance interval; that's why Adam's trying to get a more precise value. – Jacob Manaker Oct 10 '22 at 18:31
  • Okay, let's call the tolerance interval $c$ for some real constant $c$. – askquestions4 Oct 10 '22 at 18:33
  • Do you mean $c$ milligrams per day? – Adam Rubinson Oct 10 '22 at 18:35
  • I'm no expert on this, but sure, let's go with that. – askquestions4 Oct 10 '22 at 18:36
  • It's mathematically somewhat interesting so I'll give this question an upvote. I don't know if it's medically useful, although it may well be. – Adam Rubinson Oct 10 '22 at 18:43
  • Well, image you calculated that it would take 1000 years for a drug to reach the desired steady-state in your body, then you'd know something about the drug "doesn't work" and you'd have to re-evaluate the mechanism of delivery or the daily dosage. – askquestions4 Oct 10 '22 at 18:58

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Imagine you have always been taking this drug. That means at the beginning of each day after you take the drug, the total concentration of the drug will be the concentration from today's drug (let's call it $C_0$), plus what is left from yesterday, $C_0 \times 2^{-(24\, hr)/(30\, hr)}$, plus what is left of day before, $C_0 \times 2^{-(48\, hr)/(30\, hr)}$ and so on: $$ C = \sum_{k=0}^\infty C_0\times2^{-k\,(24\, hr)/(30\, hr)} = \frac{C_0}{1-2^{-24/30}}, $$ where I used the geometric series to evaluate the sum, $\sum_0^\infty x^k = \frac{1}{1-x}$.

Now if you have been only taking it for $n$ days, the total concentration at the beginning of the day would be $$ C_n = \sum_{k=0}^n C_0\times2^{-k\,(24\, hr)/(30\, hr)} = \frac{1-2^{-n\times24/30}}{1-2^{-24/30}}\times C_0. $$ Here, I used the geometric sum $\sum_0^n x^k = \frac{1-x^n}{1-x}$.

Now, you want to wait until $C_n$ is very close to $C$. Let's say $99$% close. That is $C_n/C = 99$%. That is $$ 99\%=\frac{C_n}{C} = 1-2^{-n\times24/30} $$ or $2^{-n\times24/30}=0.01$. Taking the log from both sides and solving for $n$, we have $$ n = \log(0.01)/\log\left(2^{-24/30}\right)\approx 8. $$ That is, you need to wait $8$ days to get to $99\%$ of the steady-state concentration (technically you should round up and wait for $9$ days to make sure you are within $99\%$).

More generally, if you want to be within $\epsilon$ of the steady-state value (that is $1-C_n/C=\epsilon$), you have to wait for $n=\log(\epsilon)/\log\left(2^{-24/30}\right)\approx -4.15 \times \log(\epsilon)$ days.


Update - Second solution using differential equations, as suggested by the OP:

Let us approximate the intake of the drug to be uniform throughout the day (averaged over the day), then we can write the following ODE for the change in the concentration of the drug as a function of time given by the rate of intake minus decay rate $$ \frac{dC}{dt}= \frac{C_0}{24\, hr} - \frac{\ln(2)}{30\,hr} C. $$ (Note that the factor $\ln(2)$ is needed here because half-life time is defined as the time it takes for concentration to drop by a factor of $2$, while the decay rate is the inverse time it takes for the concentration to drop by a factor $e$. In other words $e^{-(\text{decay rate})\,t} = 2^{-t/(30\, hr)}$ or decay rate $= \ln(2)/(30\, hr)$.)

This ODE has the following solution $$ C(t) = \frac{C_0\times (30\,hr)}{(24\, hr)\times \ln(2)} \left(1-2^{-\frac{t}{30\, hr}}\right). $$ The concentration at the steady state is given by $$ C_\infty \equiv \lim_{t\to\infty} C(t) = \frac{5\,C_0}{4\ln(2)}. $$ To find the time when the concentration gets withing $\epsilon$ of $C_\infty$ we set $(C_\infty- C(t))/C_\infty$ equal to $\epsilon$ and solve for $t$: $$ \epsilon = \frac{C_\infty - C(t)}{C_\infty} = 2^{-\frac{t}{30\, hr}} \implies t = -(30\, hr)\log(\epsilon)/\log(2) \\= -(30/24)\log(\epsilon)/\log(2)\, \text{days} \approx -4.15\times\log(\epsilon)\,\text{days}, $$ which is exactly what we had before.

stochastic
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  • So, technically it never reaches steady state. – user619894 Oct 10 '22 at 19:25
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    @user619894 correct, but OP is asking "within some tolerance interval." – stochastic Oct 10 '22 at 19:25
  • Thanks for your in-depth reply Stochastic. Is there a way you could rephrase the problem in terms of a differential equations? – askquestions4 Oct 10 '22 at 19:49
  • @askquestions4 yes, but it would make it unnecessarily complicated. The rate of change of concentration is given by the intake rate minus the decay rate: $dC/dt = \sum_k C_0\delta(t- k,\times, 24, hr) -C\times \ln(2)/(30 hr)$. You can solve the problem to find the full time-dependent solution which would be periodic at long time and do the same calculation I did above. I effectively used the solution of this equation only at the beginning of the day, ignoring the dynamics throughout the day. – stochastic Oct 10 '22 at 20:00
  • What if you treated the daily dosage as a sort of daily "average" throughout a 24-hour cycle? Would that simplify the ODE? – askquestions4 Oct 10 '22 at 21:45
  • @askquestions4 yes, I think that would work: $dC/dt = C_0/(24, hr) - C\times\ln(2)/(30, hr)$ solve for C and see when it reaches $99%$ of its steady state value. – stochastic Oct 11 '22 at 10:47
  • @askquestions4 see my updated answer – stochastic Oct 11 '22 at 11:48
  • @stochastic Okay, so first we determine the steady state by taking the limit to infinity (or any other subspaces), then, once we find that, we figure out how long it is until we reach 99% of that value. – askquestions4 Oct 11 '22 at 14:58