Hello NONMEM users,
The classic Michaelis-Menton model predicts the same terminal slopes for
different doses. I tried to use indirect response models to account for
different slopes, but it was not fruitful. Can you recomend a set of empirical
or mecanistic models, which predict very different terminel slopes at different
doses?
Thanks!
Pavel
Michaelis-Menten model
Pavel,
You dont give any background to help answer this question. But if the doses have different first-order absorption rates and the absorpion half-life is slower than the elimination half-life (flip-flop) then you may see dose dependent terminal half-lives.
Nick
[EMAIL PROTECTED] wrote:
> Hello NONMEM users,
>
> The classic Michaelis-Menton model predicts the same terminal slopes for different doses. I tried to use indirect response models to account for different slopes, but it was not fruitful. Can you recomend a set of empirical or mecanistic models, which predict very different terminel slopes at different doses? Thanks!
>
> Pavel
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
Thank you Zaid. After 101 atempts, I did it. One of the indirect-response models worked. There was a dose-dependent inhibition of elimination.
Pavel
Quoted reply history
----- Original Message -----
From: Hussein, Ziad
Date: Saturday, July 12, 2008 9:22 am
Subject: Re: [NMusers] Michaelis-Menten model
To: nonmem
> How about modelling the effect of dose on the terminal slope
> starting with a full exponential model with an intercept and
> reduce it further if some of the parameters are poorly estimated?
>
> Best of luck.
>
> Dr Ziad Hussein
> ICON Development Solutions
>
>
> ----- Original Message -----
> From: owner-nmusers
> To: nmusers
> Sent: Sat Jul 12 13:35:08 2008
> Subject: [NMusers] Michaelis-Menten model
>
> Hello NONMEM users,
>
> The classic Michaelis-Menton model predicts the same terminal
> slopes for different doses. I tried to use indirect response
> models to account for different slopes, but it was not fruitful.
> Can you recomend a set of empirical or mecanistic models, which
> predict very different terminel slopes at different doses?
>
> Thanks!
> Pavel
>
>
Thank you Zaid. After 101 atempts, I did it. One of the indirect-response
models worked. There was a dose-dependent inhibition of elimination.
Pavel
Quoted reply history
----- Original Message -----
From: "Hussein, Ziad (IDS UK)"
Date: Saturday, July 12, 2008 9:22 am
Subject: Re: [NMusers] Michaelis-Menten model
To: [EMAIL PROTECTED], [email protected]
> How about modelling the effect of dose on the terminal slope
> starting with a full exponential model with an intercept and
> reduce it further if some of the parameters are poorly estimated?
>
> Best of luck.
>
> Dr Ziad Hussein
> ICON Development Solutions
>
>
> ----- Original Message -----
> From: [EMAIL PROTECTED]
> To: [email protected]
> Sent: Sat Jul 12 13:35:08 2008
> Subject: [NMusers] Michaelis-Menten model
>
> Hello NONMEM users,
>
> The classic Michaelis-Menton model predicts the same terminal
> slopes for different doses. I tried to use indirect response
> models to account for different slopes, but it was not fruitful.
> Can you recomend a set of empirical or mecanistic models, which
> predict very different terminel slopes at different doses?
>
> Thanks!
> Pavel
>
>