7 replies to this topic

[yongcertara]

Dear Useers,

Assume a range of doses (0-50mg/kg) resulted TGI (tumor growth inhition) from 0-100% in mice xenograft after once a day treatment for 10 days.

deriv(E = Kng*E-E*Kmax*C/(KC50+C)) was ued to model the tumor kill. 

PK model was freezed.

 

How to make a TGI vs Concentration plot based on tumor Xenograt data shown below??

I assume the concentration shown in the figure below was Css

Thank you so much.

 

 

 

[cradhakr]

Hi,

 

Did you get a chance to look at our PML code for the tumor growth/kill model?

 

https://support.cert...mor-growthkill/

 

The codes are available for Gompertz, Simeoni, Jumbe models. Also, there are no data attached showing TGI Vs Concentration.

 

Thanks

Mouli

[yongcertara]

Hi Mouli,

I watched the PML school tumor kill lecture, which is very helpful.

I modeled the tumor kill by using deriv(E = Kng*E-E*Kmax*C/(KC50+C)) . I solved all fixed effect parameters.

Now, I want to know how to correlate drug plasma concentration with TGI as shown in the figure below. So, I can estimate the concentration required for certain TGI, and then use that concentration to project effective concentration in humans. 

The figure below was the figure-6b from the attached reference.

 

[yongcertara]

I pasted the figure but it disappeared again after I posted it.

Please see figure-6b in the attached reference.

Many thanks

Attached Files

•  Yamazaki 2014 rebound Emax Kng 000.pdf   1.23MB   198 downloads

[cradhakr]

Hi Yongcertara,

 

Thanks for sharing the publications. Have you developed the model? if so is it possible for you to share the project file/code. If you don't wanted this to be posted on the forum please send it to support@certara.com.

 

This will save me time to work on the model rather than building from the scratch.

 

Thanks

Mouli

[yongcertara]

Hi Mouli,

Please see model below. Many Thanks

 

test(){

deriv(Aa = - Ka * Aa)

deriv(A1 = Ka * Aa - Cl * C)

dosepoint(Aa)

C = A1 / V

 

stparm(Ka = tvKa)

stparm(V = tvV)

stparm(Cl = tvCl)

fixef(tvKa(freeze) = c(, 0.22, ))

fixef(tvV(freeze) = c(, 35487, ))

fixef(tvCl(freeze) = c(, 7643, ))

 

 

deriv(E = Kng*E-E*Kmax*C/(KC50+C))

 

error(EEps = 1)

observe(EObs = E + EEps)

sequence{E=200}

stparm(Kng = tvKng)

stparm(Kmax = tvKmax)

stparm(KC50 = tvKC50)

 

fixef(tvKng = c(, 0.0066, ))

fixef(tvKmax = c(, 0.0084, ))

fixef(tvKC50 = c(, 70, ))

 

 

}

[f_yc]

Hi Mouli,

I watched the PML school tumor kill lecture, which is very helpful.

I modeled the tumor kill by using deriv(E = Kng*E-E*Kmax*C/(KC50+C)) . I solved all fixed effect parameters.

Now, I want to know how to correlate drug plasma concentration with TGI as shown in the figure below. So, I can estimate the concentration required for certain TGI, and then use that concentration to project effective concentration in humans. 

The figure below was the figure-6b from the attached reference.

 

Hi yongcertara,

 

It's very simple, maybe I'll transform your formula for you and you'll understand.

 

Old formula:

deriv(E = Kng*E-E*Kmax*C/(KC50+C))

 

New formula:

deriv(E = Kng*E-E*TGI)

TGI=Kmax*C/(KC50+C)

 

Pharmacokinetics books are a very good guide. Flip through it when you encounter confusion and you will get the answer.

 

Sincerely,

f_yc

[yongcertara]

 

Hi yongcertara,

 

It's very simple, maybe I'll transform your formula for you and you'll understand.

 

Old formula:

deriv(E = Kng*E-E*Kmax*C/(KC50+C))

 

New formula:

deriv(E = Kng*E-E*TGI)

TGI=Kmax*C/(KC50+C)

 

Pharmacokinetics books are a very good guide. Flip through it when you encounter confusion and you will get the answer.

 

Sincerely,

f_yc

 

Hi f_yc.

Thank you again,

Kng=0.0066 and Kmax=0.0084 in this case, therefore "TGI=Kmax*C/(KC50+C)" may not do the trick in my understanding.

Your formular works if Kmax=1.

Thanks