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Re: [NMusers] Help with a PK code

From: Niurys.CS <amaranthfan_at_gmail.com>
Date: Thu, 25 Apr 2019 08:21:38 -0500

Dears Leonid and Saeheum,

First of all, thank you for your suggestions, they are very useful and
cleared up some queries I had.
Leonid, regarding your question about measurement of free or total
ligand concentration, in this study we only measured the free ligand
concentration.

Thank so much,
Regards,
Niurys


2019-04-23 12:00 GMT-05:00, Leonid Gibiansky <lgibiansky_at_quantpharm.com>:
> The code will work as written (if you add ENDIF after TVVM = THETA (6)=
,
> and define all parameters CL, V1, Q, V2, KINT, ...) but mechanistically,
> this is not a good idea to have two models for two dose levels. You may
> want to try QSS model with non-constant Rtot (MM model is usually good
> when Rtot is low, while QSS is good when Rtot has accumulation, so may
> be this is why you see MM model at low doses and QSS at high doses).
>
> Also, what is measured, is it free or total concentration? This part of
> the code was not shown, and it depends on the assay (for QSS part of the
> model).
>
> Thanks
> Leonid
>
>
> On 4/23/2019 8:34 AM, Niurys.CS wrote:
>> Dear All,
>>
>> I'm working on the population pharmacokinetics of a mAb, in this study
>> 4 dose levels (50, 100, 200 and 400 mg) were evaluated. I tested
>> different models, but none of them fit well; that's why I decided to
>> find for each dose level the best model. I found the two lower dose
>> levels fitted to Michaelis Menten + CL linear model and the two higher
>> dose levels fitted to QSS Rtot model.
>> I think if I use this code, I'll find the best model for my data, so I
>> appreaciate your suggestions:
>>
>> $PK
>>
>> TVCL= THETA(1)
>> TVV1= THETA(2)
>> TVQ = THETA(3)
>> TVV2 = THETA (4)
>>
>> TVKM = 0
>> TVVM = 0
>>
>> IF(DOS.LT.200) THEN
>> TVKM = THETA (5)
>> TVVM = THETA (6)
>>
>> TVKSS = 0
>> TVKINT = 0
>> TVKDEG = 0
>> TVRMAX = 0
>>
>> IF(DOS.GT.100) THEN
>>
>> TVKSS = THETA (7)
>> TVKKINT = THETA(8)
>> TVRMAX = THETA(9)
>>
>> ENDIF
>>
>>
>> K = CL/V1
>> K12 = Q/V1
>> K21 = Q/V2
>> S1 = V1
>>
>> ;----------------------------------
>> $DES
>>
>> CONC=0.5*(A(1)/V1-RMAX-KSS)+0.5*SQRT((A(1)/V1-RMAX-KSS)**2+4*KSS*A(1)/=
V1)
>>
>> DADT(1) =
>> -(K+K12)*CONC*V1+K21*A(2)-KINT*RMAX*CONC*V1/(KSS+CONC)-VM*CONC*V1/(KM+CO=
NC)
>> DADT(2) = K12*CONC*V1-K21*A(2)
>>
>>
>> Thank you,
>>
>> Regards,
>> Niurys de Castro
>>
>


--

MSc Niurys de Castro Suárez
Profesor Asistente FarmacometrĂ­a
Investigador Agregado
Departamento Farmacia
Instituto de Farmacia y Alimentos, Universidad de La Habana
Cuba
"Una estrella brilla en la hora de nuestro encuentro"

Received on Thu Apr 25 2019 - 09:21:38 EDT

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