RE: Assessment of elimination half life of mAb
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 therapy. We go
back to them and say, we can't give you a half-life because it's a nonlinear
drug, but once the kinetics become linear the half-life is X hours. That is a
terrible answer. Maybe we need to come up with a new term, call it C90, the
time it takes for Cmax to decline by 90%. That we can do. We don't even need
an analytical solution, we can eyeball it. We could even get fancy and do it
in a population model. C90 - the time it takes for Cmax to decline 90% in 90%
of patients. Of course, for nonlinear drugs, C90 only holds for that dose.
Change in dose results in a new C90. Just a thought.
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
[email protected]
(224) 619-4901
It’s been a while since I’ve had something here, but here is a Dad joke.
Question: Do you know why the math book was sad?
Answer: Because it had so many problems
Quoted reply history
-----Original Message-----
From: [email protected] <[email protected]> On Behalf Of
Leonid Gibiansky
Sent: Thursday, April 29, 2021 9:54 AM
To: Niurys.CS <[email protected]>
Cc: [email protected]
Subject: Re: [NMusers] Assessment of elimination half life of mAb
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
> go into this topic in any depth.
> Best,
> Niurys
>
> El 28/04/2021 19:34, "Leonid Gibiansky" <[email protected]
> <mailto:[email protected]>> escribió:
>
> There is no such thing as half-life of elimination for the nonlinear
> drug. But one can compute something like half-life:
>
> 1. Half-life of the linear part (defined by CL, V1, V2, Q): this
> defines the half-life at high doses/high concentrations when
> nonlinear elimination is saturated.
>
> 2. Washout time: for the linear drug, 5 half-lives can be used to
> define washout time. During this time, concentrations drop
> approximately 2^5=32 times. So one can simulate the desired dosing
> (single dose or steady state), find the time from Cmax to Cmax/32
> and call it washout time (or time to Cmax/64 to be conservative)
>
> Thanks
> Leonid
>
>
> On 4/28/2021 5:17 PM, Niurys.CS wrote:
>
> Dear all
> I need some help to assess the elimination half life of a
> monoclonal antibody.
> The model that describes the data is a QSS aproximation of TMDD
> with Rmax constant. The model includes two binding process of
> mAb to its target: in central and peripheral compartments.
> Is there any specific equation to calcule lambda z and the
> elimination half life for each of the TMDD aproximations?
> Thanks
> Niurys
>