# Re: Prednisone and Prednisolone PPK

From: Alice Nichols <NICHOLA2>
Date: Fri, 05 Dec 2008 10:50:20 -0500

setting a nonlinear CL from prednisone to prednisolone is probably a =
reasonable fix, a hill equation instead of just estimating a Cl could =
work, although you'd probably need to fix one of the terms in the hill =
equation since data is limited

Alice.

Alice I Nichols, PhD
Sr Director
Early Development and Clinical Pharmacology
Wyeth Research
500 Arcola Rd
Collegeville, PA 19426
tel: 484-865-8741/ fax: 484-865-9075
nichola2

>>> "Chandrasekhar Udata" <Udatac

Dear all,

I am working on modelling prednisone and prednisolone PPK in humans given =
a PO dose of prednisone. Note that prednisone is converted to prednisolone =
during the first-pass and prednisolone is converted back to prednisone =
(reversible metabolism). I used a simple 2-cmt PK model (see the code =
below) that seems to work. However, the model does not appear to be =
stable and sensitive to initial estimates . Is there an issue of "identifia=
bility" in this model? does anyone has already worked on PPK of this drug? =
Furthermore, I would like to model the inhibition of conversion of =
prednisone to prednisolone as function of time and test drug concentration.=

Regards,
- Chandra

----------------------------------------------------------------------

\$INPUT C ID TIME DV AMT CMT EVID MDV
\$DATA pred2.CSV IGNORE=C
\$MODEL NPAR=7 NCOMP=3
COMP=(DEPOT,DEFDOSE)
COMP=(PARENT)
COMP=(METAB)

\$PK

KA=THETA(1)*EXP(ETA(1))
VP=THETA(2)*EXP(ETA(2))
CLP=THETA(3)*EXP(ETA(3))
VMT=THETA(4)*EXP(ETA(4))
KF=THETA(5)*EXP(ETA(5))
KB=THETA(6)*EXP(ETA(6))
CLM=THETA(7)*EXP(ETA(7))

S2=VP
S3=VMT

\$DES

\$ERROR
FLAG=0
IF(AMT.NE.0) FLAG=1
IPRED=LOG(F+FLAG)
R1=0
IF (CMT.EQ.2) R1=1
R2=0
IF (CMT.EQ.3) R2=1
Y2=IPRED+ERR(1)
Y3=IPRED+ERR(2)
Y=R1*Y2+R2*Y3
IRES=EXP(DV)-EXP(IPRED)

\$THETA .......

\$OMEGA .......

\$SIGMA .......

\$EST SIG=5 METHOD=1 PRINT=1 MAX=9999 POSTHOC NOABORT

Received on Fri Dec 05 2008 - 10:50:20 EST

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