Re: 3 compartment nonlinear pharmacokinetics model

From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: [NMusers] 3 compartment nonlinear pharmacokinetics model Date: Wed, 14 Nov 2001 09:47:29 +1300 Yungwei Hsu wrote: > > Dear all, > > I am trying to model a 3 compartment nonlinear PK model. The drug's > elimination rate is concentration-dependent. Increasing concentration > decreases the clearance. My experiment is based on a computer controlled > infusion program to target plasma concentration at 4 different steady state > levels, each level last 40 min. Two pk data were collected in each step and > also series of recovery pk data were collected. > > Could somebody provide me a template of control file to model this problem? Assuming you know how to set up the data file for a linear PK problem then you can use the same data format. The model code could look like the following. Note that PREDPP will take care of the input into compartment one. You should not add a term to the DADT(1) expression for the infusion input. Also because of an NONMEM naming convention you cannot use the same variable name in $DES and $ERROR which is why I use DC1 in $DES and C1 in $ERROR. $SUBR ADVAN6 TOL=5 $MODEL COMP (ONE) COMP (TWO) COMP (THREE) $PK V1=THETA()*EXP(ETA()) VMAX=THETA()*EXP(ETA()) KM=THETA()*EXP(ETA()) V2=THETA()*EXP(ETA()) Q2=THETA()*EXP(ETA()) V3=THETA()*EXP(ETA()) Q3=THETA()*EXP(ETA()) $DES DC1=A(1)/V1 DC2=A(2)/V2 DC3=A(3)/V3 CL=VMAX/(KM+DC1) DADT(1)=Q2*DC2 + Q3*DC3 - (Q2 + Q3 + CL) *DC1 DADT(2)=Q2*(DC1-DC2) DADT(3)=Q3*(DC1-DC3) $ERROR C1=A(1)/V1 Y=C1*EXP(ERR()) + ERR() Your data set seems VERY sparse so dont expect too much from trying to fit this model. Nick -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/