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Table of contents

Nizatidine case study

Nizatidine practice problem

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Nizatidine case study

The data shown below are mean values obtained from the publication:

Callaghan JT, Bergstrom RF, Obermeyer BD, King EP, Offen WW, Intravenous nizatidine kinetics and acid secretion. Clin. Pharmacol. Ther. 37: 162-165 (1984) [Pubmed] [Full text]

Nizatidine exhibits linear kinetics with CL = 46 L/hr and V = 1.2 L/kg in normal male subjects.
Gastric acid secretion was stimulated with pentagastrin prior to intravenous administration of various doses of nizatidine as 5-min. infusions.

Only one dose level (250 mg) fitting is shown here

WinNonlin code: indirect response pharmacodynamic model

MODEL
COMMANDS

NFUNCTIONS 1
NDERIVATIVES 1
NPARAMETERS 4
PNAMES 'kout','Ro','IC50','Imax'
NSECONDARY 1
SNAMES 'kin'

END
TEMPORARY

T=X
D1= 250000
V= 84
CL=46
kin=Ro*Kout
C1 = D1/V*exp(-CL/V*T)
IHF1 = Imax*C1/(C1+IC50)

END
START

Z(1) = Ro

END
DIFFERENTIAL

DZ(1) = kin*(1-IHF1)-kout*Z(1)

END
FUNCTION 1

F= Z(1)

END
SECONDARY

kin=Ro*kout

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)

 

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Nizatidine practice problem

Propose a PK/PD model for these data and generate estimates of relevant parameters.
Fit data for all dose levels.

Click here to download dataset in EXCEL format

Click here to download dataset in WinNonlin format (will be available after the course)

Click here to download WinNonlin code (will be available after the course)

Submit two pages with commentary. Show your WinNonlin or Adapt program steps.

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