Transduction model

The new therapeutic agent, Trandosyn (Dose = 100 mg), was administered to rats and the following pharmacokinetic and pharmacodynamic data were generated. The Response data reflect activities of an enzyme responsible for lipid metabolism in the liver.

Propose a PK/PD model and provide estimates of suitable model parameters.

WinNonlin code: Transduction model

MODEL
COMMANDS

NFUNCTIONS 1
NDERIVATIVES 5
NPARAMETERS 3
PNAMES 'EMAX', 'EC50', 'TAU'

END
TEMPORARY

T=X
E0=0.09
D=100
V=2.41
CL=1.3
C=D/V*EXP(-CL/V*T)

END
START

Z(1) = 0
Z(2) = 0
Z(3) = 0
Z(4) = 0
Z(5) = 0

END
DIFFERENTIAL

DZ(1) = 1/TAU*(EMAX*C/(EC50+C)-Z(1))
DZ(2) = (Z(1)-Z(2))/TAU
DZ(3) = (Z(2)-Z(3))/TAU
DZ(4) = (Z(3)-Z(4))/TAU
DZ(5) = (Z(4)-Z(5))/TAU

END
FUNCTION 1

F= E0+Z(5)

END
EOM

WinNonlin dataset (click here) Save the dataset to hard disk to open with WinNonlin

WinNonlin stepwise model run (click here)

WinNonlin output (click here)

---

Go to main page