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From: Leonid Gibiansky <lgibiansky_at_quantpharm.com>

Date: Tue, 23 Apr 2019 13:00:24 -0400

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+CONC)
*

*> DADT(2) = K12*CONC*V1-K21*A(2)
*

*>
*

*>
*

*> Thank you,
*

*>
*

*> Regards,
*

*> Niurys de Castro
*

*>
*

Received on Tue Apr 23 2019 - 13:00:24 EDT

Date: Tue, 23 Apr 2019 13:00:24 -0400

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:

Received on Tue Apr 23 2019 - 13:00:24 EDT