Half-life is more relevant for first-order kinetics. For nonlinear PK,
half-life changes with concentration (~dose) and thus is not useful. As
David pointed out, phenytoin is a good example for this. We use the
Michaelis-Menten (MM) equation for dose calculations in case of phenytoin.
In that,
A simulation like https://www.boomer.org/c/p4/js/w200101/index1.php
For example use Dose = 500, V1 = 25, Vm = 200 and Km = 5, Max X = 148 and
semi-log. Compare with Vm = 160 and Km = 4. Same terminal slope, t(1/2)
approximately 10 hr.
BTW, NCA isn’t very good for non linear PK. Not sure that
Dear all,
I'm very grateful for these ideas and explanations. Actually, I was worry
about this topic. Previously, I reported the values of half life by NCA;
however the clinicians are asking for a half life value estimated by
population PK.
Many thanks to you in the name of Cuban team.
Niurys
El
Hi Leonid,
First of all thanks for your response saying half-life has no useful meaning
for a drug with non-linear PK (clearance and/or volume, plasma protein binding,
etc).
Half-life is a useful parameter for some simple cases but when the question
about the time course of drug effect then
All I can say is, Great minds.
Maybe some of these ideas can help you, Niurys.
pete
Peter Bonate, PhD
Executive Director
Pharmacokinetics, Modeling, and Simulation (PKMS)
Clinical Pharmacology and Exploratory Development (CPED)
Astellas
1 Astellas Way, N3.158
Northbrook, IL 60062
still, half-life of the linear part could be helpful in cases when
non-linearity plays no significant role in elimination, so we tend to
present it together with the washout time simulations.
Leonid
On 4/29/2021 12:35 PM, Justin Wilkins wrote:
Hi Bill, all,
I do much the same thing - when
Hi Bill, all,
I do much the same thing - when there's nonlinearity happening, I've found it
to be effective to plot concentration-time curves by doses and regimens of
interest and mark the times at which the (median?) clinically-defined threshold
for "washout" has been reached in each case. Of
To Bill and Pete and all -
Just adding my experience
I agree that a simulation based "time - to - x%" endpoint are very useful. -
half life means very little or is distracting.
Myself, I have used such simulations to establish label language for
prescribers for an injectable product with
Hi Pete,
I agree that it is hard to communicate. I like the general idea of C90 you
propose. I tend to choose something in between your and Leonid's answer,
when possible. I target an answer of "when is the pharmacodynamic effect
<5% of the maximum or therapeutic effect". It does require more
I've never really been happy with this. It's an unsatisfactory solution. You
have a nonlinear drug. Let's assume you have an approved drug. It's given at
some fixed dose. The clinician wants to know what is the drug's half-life so
they can washout their patient and start them on some other
I am not aware of any papers specifically addressing the half-live
issue, but there are tons of original papers and tutorials on TMDD, just
search the web
Thanks
Leonid
On 4/29/2021 9:48 AM, Niurys.CS wrote:
Dear Leonid,
Many thanks for clearing up my doubt. Can you suggest me any paper to
Dear Leonid,
Many thanks for clearing up my doubt. Can you suggest me any paper to go
into this topic in any depth.
Best,
Niurys
El 28/04/2021 19:34, "Leonid Gibiansky"
escribió:
> There is no such thing as half-life of elimination for the nonlinear drug.
> But one can compute something like
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