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Intro to PML School and Lesson 1 on nonlinear clearance

PML clearance

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#21 LLLi

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Posted 25 October 2016 - 07:12 PM

Hi,

 

I am looking through the PK 24 in Dr. Weiner's book (4th edition, page 698). I have some questions that are not related to the code: how to get the initial estimate of alpha, beta and gamma besides using NCA and PK built-in model? I didn't find the numbers of the equation 24:5 to 24:7 in the dataset. Could someone provide more details about the initial estimates?

Furthermore, can we use graphic model for this dataset?

 

Thank you!

 

LLLi


Edited by LLLi, 25 October 2016 - 07:34 PM.


#22 dlweiner

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Posted 25 October 2016 - 08:44 PM

Hi,

 

I am looking through the PK 24 in Dr. Weiner's book (4th edition, page 698). I have some questions that are not related to the code: how to get the initial estimate of alpha, beta and gamma besides using NCA and PK built-in model? I didn't find the numbers of the equation 24:5 to 24:7 in the dataset. Could someone provide more details about the initial estimates?

Furthermore, can we use graphic model for this dataset?

 

Thank you!

 

LLLi

LLLi,

 

To obtain initial estimates for this model, one would need to manually derive them using exponential curve stripping.  Alternatively, you could map your data to the Classic WNL PK Model 19.  When using Classic WNL models, the program can derive its own initial estimates (single dose data only).  Hopefully this functionality will be added to Phoenix WNL in a future release.  So for PK24, you could start by fitting the static CL model 19 using classic WNL, and then switch to Phoenix WNL for the nonlinear clearance model using the final parameter estimates from Model 19.  There is no need to use the graphical model (although one could) as you can fit a 3 compartment model directly using the model library with Phoenix WNL.

 

Dan Weiner



#23 bwendt@certara.com

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Posted 26 October 2016 - 11:47 AM

Bernd,

 

Is the 5th edition of Gabrielsson and Weiner available? It can be bought on Amazon but the shipping date is December to January.

 

Bruno

 

Bruno,

 

we got information from the publisher, please see below:

 

"During the summer we had a message at Amazon that delivery could take up to two months (due to vacations), this message has accidently remained into the autumn (however the actual delivery time has been one week). We have now removed the message."

 

So you should get it within a week's time.

 

Bernd



#24 mittyright

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Posted 27 October 2016 - 01:18 PM

LLLi,

 

To obtain initial estimates for this model, one would need to manually derive them using exponential curve stripping.  Alternatively, you could map your data to the Classic WNL PK Model 19.  When using Classic WNL models, the program can derive its own initial estimates (single dose data only).  Hopefully this functionality will be added to Phoenix WNL in a future release.  So for PK24, you could start by fitting the static CL model 19 using classic WNL, and then switch to Phoenix WNL for the nonlinear clearance model using the final parameter estimates from Model 19.  There is no need to use the graphical model (although one could) as you can fit a 3 compartment model directly using the model library with Phoenix WNL.

 

Dan Weiner

Dear Dan!

 

It is not obligatory to use Classic WNL model to derive initial estimates. All WNL models are embedded to the Phoenix model, you can push a 'Set WNL' button and choose the model 19. In my experience even from default starting position (all parameters are equal to 1) the PHX 7 algo produces more precise values of Final parameters (alpha beta gamma) than classical WNL object.



#25 LLLi

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Posted 27 October 2016 - 02:46 PM

Dear Dan!

 

It is not obligatory to use Classic WNL model to derive initial estimates. All WNL models are embedded to the Phoenix model, you can push a 'Set WNL' button and choose the model 19. In my experience even from default starting position (all parameters are equal to 1) the PHX 7 algo produces more precise values of Final parameters (alpha beta gamma) than classical WNL object.

Hi mittyright,

I used the "set WNL" button and choose the model 19 as you mentioned but get the message "the model execution failed or cancelled". Would you please take a look at my project attached? I am still using PHX6.4 and am not sure it is the reason.

Thank you!

LLLi

Attached Files



#26 LLLi

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Posted 27 October 2016 - 03:04 PM

LLLi,

 

To obtain initial estimates for this model, one would need to manually derive them using exponential curve stripping.  Alternatively, you could map your data to the Classic WNL PK Model 19.  When using Classic WNL models, the program can derive its own initial estimates (single dose data only).  Hopefully this functionality will be added to Phoenix WNL in a future release.  So for PK24, you could start by fitting the static CL model 19 using classic WNL, and then switch to Phoenix WNL for the nonlinear clearance model using the final parameter estimates from Model 19.  There is no need to use the graphical model (although one could) as you can fit a 3 compartment model directly using the model library with Phoenix WNL.

 

Dan Weiner

Dear Dr. Weiner,

Thank you for your reply.

I have a question about PK23 (also nonlinear kinetic-flow, only contains data of Ca, Cav and QH).

I am wondering if we still can use PML to deal with this application since we first need to choose a model in NLME.

Furthermore, how to get the initial estimates of eps and DN?

Thank you!

P.S. the 5th edition from apotekarsocieteten.se is on the way and can't wait to read the new book!

LLLi


Edited by LLLi, 27 October 2016 - 03:58 PM.


#27 mittyright

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Posted 27 October 2016 - 04:56 PM

Hi mittyright,

I used the "set WNL" button and choose the model 19 as you mentioned but get the message "the model execution failed or cancelled". Would you please take a look at my project attached? I am still using PHX6.4 and am not sure it is the reason.

Thank you!

LLLi

 Dear LLLi,

 

you need to specify A1Strip. That's a consequence of Macro model usage.

Please see the User's Guide:

The meaning of stripping dose: The Macro model has a sum of exponentials that
are fitted to the original observed value of C, using some original dose, whatever
it is. If the model is again fitted against data obtained at another time with a
higher or lower dose, then the question is how to make the model predict higher
or lower values of C. This is done by multiplying the model's predicted value of C
by a ratio of the current dose and the original dose. The value used for the original
dose is called the “stripping dose”, and it allows the model to be used with
dose values and sequences different from the original.
 
So you can put in A1Strip the same value as for A1 to make it work


#28 xli@levenabiopharma.com

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Posted 23 September 2020 - 11:58 PM

Hi All experts,

 

I am confused by the lesson 1 I played it in the morning. I am a new Phoenix user and want to know this software as much as possible. after I heard the video of lesson 1, I even do not know how to use this software.

 

To my experience, I just use the model well build in the software system. I do not know anything about a, A1, Cl10, Cl and so on.

 

May I ask you a favor to give me the basic information for the lesson 1?

 

highly appreciate your help!

 

xiaoqing



#29 Simon Davis

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Posted 24 September 2020 - 07:53 AM

Hi Xiaoqing, if you want to learn some basics I would look at Certara University, we have several free and paid for courses

 

this one is a quiz to help find the best entry point(s) into the learning program.

https://www.certarau...7937967/details

 

the user documentation will also tell you how to do something and the tutorial videos should help as well.

 

https://onlinehelp.c...s= &rhhlterm=A1

 

A1 is normally the amount in the central compartment and for instantaneous bolus IV dosing would be equal to the dose at time 0.  But I think you need to learn to 'walk before you run' ! ;0)

Simon.



#30 xli@levenabiopharma.com

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Posted 24 September 2020 - 04:31 PM

Hi Simmon,

 

Thank you very much for your quick response.

 

The link told me that I did not have authorization to open it.

 

Thank you very much again!

 

Hi Xiaoqing, if you want to learn some basics I would look at Certara University, we have several free and paid for courses

 

this one is a quiz to help find the best entry point(s) into the learning program.

https://www.certarau...7937967/details

 

the user documentation will also tell you how to do something and the tutorial videos should help as well.

 

https://onlinehelp.c...s= &rhhlterm=A1

 

A1 is normally the amount in the central compartment and for instantaneous bolus IV dosing would be equal to the dose at time 0.  But I think you need to learn to 'walk before you run' ! ;0)

Simon.

Hi Simmon,

 

Thank you very much for quick response.

 

But I could not open the link for quiz because it told me that I do not have the authorization.

 

xiaoqing



#31 xli@levenabiopharma.com

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Posted 24 September 2020 - 04:32 PM

Hi Simmon,

 

Thank you very much for your quick response.

 

The link told me that I did not have authorization to open it.

 

Thank you very much again!

 

Hi Simmon,

 

Thank you very much for quick response.

 

But I could not open the link for quiz because it told me that I do not have the authorization.

 

xiaoqing

Sorry for misspelled your name.






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