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Re: simluation Tmax Cmax AUC

From: David Foster <David.Foster>
Date: Fri, 23 Apr 2010 08:35:34 +0930

Hello,

Perhaps this paper might be useful:

C Dansirikul, M Choi, SB Duffull Computers in Biology and Medicine 35 (2005) 389 – 403 “Estimation of pharmacokinetic parameters from non-compartmental variables using Microsoft Excel”.

Abstract:
***
This study was conducted to develop a method, termed ‘back analysis (BA)’, for converting non-
compartmental variables to compartment model dependent pharmacokinetic parameters for both one- and
two-compartment models. A Microsoft ExcelJ spreadsheet was implemented with the use of Solver J and
visual basic functions. The performance of the BA method in estimating pharmacokinetic parameter values
was evaluated by comparing the parameter values obtained to a standard modelling software program, NON-
MEM, using simulated data. The results show that the BA method was reasonably precise and provided
low bias in estimating fixed and random effect parameters for both one- and two-compartment models. The
pharmacokinetic parameters estimated from the BA method were similar to those of NONMEM estimation.
***

I have employed the technique myself and found it to very useful.

Regards,

David


On 23/04/10 1:19 AM, "yhb5442387" <yhb5442387

Dear Sebastien:
I have to say that my admiration to you is beyond the words,because you have directly pointed out the radical essence.Could the ke or the V/F,any one , be derived from the known Cmax,AUC,?As far as I have leaned ,the equations are as follows:
AUC=Dose*F/Ke*V,
Cmax=(F*Dose/V)*(exp(Ka*Tmax)-epx(Ke*Tmax)).
After the computation and transformation ,I was obstructed in the front of the following
: Ke-2.1*Ln(Ke)=3.18.
something like that, well I could not remember the constant number (2.1 e.g.) clearly. I am not able to solve that equation.
So,I decide to make some equations in the $PK,in which the CL V and Ka could all be expressed as the component of Tmax ,Cmax,and AUC at the same time.The suggestion you have made is usefull,but still a little problem :the Ke.
Thank you for your generous help.
22 03:24:55,"Sebastien Bihorel" <Sebastien.Bihorel
>
>It looks like you are trying to derive the unknown values of KA, CL/F
>and V/F from the known values of Tmax, Cmax and AUC (probably obtained
>from a non compartmental analysis).
>
>If that is really the case, you will need to know the values of the
>half-life of elimination or the slope of elimination Ke to solve for Ka
>and V/F (the following solutions assume a one-compartment model with
>linear absorption and elimination):
>
>CL/F = Dose/AUC
>
>V/F = (CL/F)/Ke
>
>KA = - (1/tmax)*ln[ exp(-ke*tmax) - (Cmax*V)/(F*dose) ]
>
>If you don't know Ke, you will have to solve for V/F and Ka numerically,
>prior to your simulation.
>
>Sebastien
>
>yhb5442387 wrote:
>>
>> Dear Nmuser:
>>
>> I would like to do a data simulation .The distributions of the drug
>> population pharmaockinetics were assumed to be normal.But the profile
>> that I have got is Tmax, Cmax,and AUC(the means and variances are
>> already known),instead of Ka,CL,and V. What the $PK modification
>> should I have to do in the model where the advan2 has been taken in
>> the $subroutine.
>>
>> F=1.
>>
>> Any suggestion would be appreciated.
>>
>> Yours,ye hong bo
>>
>>
>>
>>
>> --
>> 工作和生活,都要开心的过.
>> 你好,叶红波在此送上真挚的祝福.祝你开心,
>> 叶红波
>>
>>


--
工作和生活,都要开心的过.
你好,叶红波在此送上真挚的祝福.祝你开心,
                    叶红波







David Foster, PhD
Lecturer

School of Pharmacy and Medical Sciences
Playford Building
Room P4-08
City East Campus
University of South Australia
Adelaide SA 5000
CRICOS Provider Number: 00121B
Phone: +61 8 8302 2055
Fax: +61 8 8302 2389
Email: david.foster

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Received on Thu Apr 22 2010 - 19:05:34 EDT

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