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

Phoenix Certara Forums Phoenix WNL basics
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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 = KngE-EKmax*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.

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Hi,

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

https://support.certara.com/forums/topic/1040-lesson-13-modeling-tumor-growthkill/

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

Thanks

Mouli

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Hi Mouli,

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

I modeled the tumor kill by using deriv(E = KngE-EKmax*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.

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

Please see figure-6b in the attached reference.

Many thanks

Yamazaki 2014 rebound Emax Kng 000.pdf (1.23 MB)

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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

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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 = KngE-EKmax*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, ))

}

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Hi yongcertara,

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

Old formula:

deriv(E = KngE-EKmax*C/(KC50+C))

New formula:

deriv(E = KngE-ETGI)

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

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