---

Table of contents

Pharmacokinetics

Direct effect linear pharmacodynamic model

Direct effect simple Emax pharmacodynamic model

Direct effect sigmoidal Emax pharmacodynamic model

Pharmacokinetic delayed effect (Effect compartment) Emax pharmacodynamic model

---

Case study

Simulation study design

Dose levels (4)- 5,50, 100, 250 mg intravenous administration

Sampling: every hour until 24 hours post dosing

One compartment body model with first order elimination

Clearance: 0.5 L/hr

Central compartment volume of distribution: 1 L

Pharmacokinetics

 

---

Direct effect linear pharmacodynamic model

 

WinNonlin code: direct effect linear pharmacodynamic model

Model

COMMANDS

   NFUNCTIONS 1

   NPARAMETERS 1

   PNAMES  'Slope'

END

TEMPORARY

   Slope=P(1)

   CONC=X

END

FUNCTION 1

   F= Slope*CONC

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)

---

Direct effect simple Emax pharmacodynamic model

 

Effect of Emax

Three  Emax levels (low= 10, moderate= 50 and high= 100) are used.

WinNonlin code: Direct effect Emax pharmacodynamic model

 

Model

COMMANDS

   NFUNCTIONS 1

   NPARAMETERS 2

   PNAMES  'Emax', 'EC50'

END

TEMPORARY

   Emax=P(1)

   EC50=P(2)

   CONC=X

END

FUNCTION 1

   F= Emax*CONC/(EC50+CONC)

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)

---

Direct effect sigmoidal Emax pharmacodynamic model

 

 

WinNonlin code: Direct effect sigmoidal Emax pharmacodynamic model

Model

COMMANDS

   NFUNCTIONS 1

   NPARAMETERS 3

   PNAMES  'Emax', 'EC50', 'Gamma'

END

TEMPORARY

   Emax=P(1)

   EC50=P(2)

   Gamma=P(3)

   CONC=X

END

FUNCTION 1

   F= Emax*CONC**Gamma/(EC50**Gamma+CONC**Gamma)

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)

 

---

 

Pharmacokinetic delayed effect (Effect compartment) Emax pharmacodynamic model

 

 

WinNonlin code: Effect compartment Emax pharmacodynamic model

Model

COMMANDS

NFUNCTIONS 4
NDERIVATIVES 8
NPARAMETERS 3
NCONSTANTS 6
PNAMES 'Ke0', 'Emax', 'EC50'

END
TEMPORARY

T=X
CL=CON(1)
V=CON(2)
DOSE1=CON(3)
DOSE2=CON(4)
DOSE3=CON(5)
DOSE4=CON(6)
K= CL/V

END

START

Z(1) = DOSE1/V
Z(2) = 0
Z(3) = DOSE2/V
Z(4) = 0
Z(5) = DOSE3/V
Z(6) = 0
Z(7) = DOSE4/V
Z(8) = 0

END
DIFFERENTIAL

DZ(1) = -K*Z(1)
DZ(2) = Ke0*((Z(1)/V)-Z(2))
DZ(3) = -K*Z(3)
DZ(4) = Ke0*((Z(3)/V)-Z(4))
DZ(5) = -K*Z(5)
DZ(6) = Ke0*((Z(5)/V)-Z(6))
DZ(7) = -K*Z(7)
DZ(8) = Ke0*((Z(7)/V)-Z(8))

END
FUNCTION 1

F= Emax*Z(2)/(EC50+Z(2))

END
FUNCTION 2

F= Emax*Z(4)/(EC50+Z(4))

END
FUNCTION 3

F= Emax*Z(6)/(EC50+Z(6))

END
FUNCTION 4

F= Emax*Z(8)/(EC50+Z(8))

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)

WinNonlin output using explicit solution (same dataset and steps) (click here)

---

Go to main page

---