From: Indranil Bhattacharya <*ibhattacharya*>

Date: Wed, 10 Feb 2010 00:04:48 -0500

Hi, I have a question regarding how NONMEM reads the code when doing a

sequential PK/PD run.

I fit the PK data (extravascular admin) using a KOKA model with sequential

absorption. The data was based described by this sequential model where K0

process starts after Ka. To fit the data I used ADVAN4 TRANS4 (2 COMP

model).

Now the next step is to fit the PD data and here is where I am confused.

For the PK parameters I designate them under $PK as shown in the code

provided. CL and V2 had individual values which were included in the data

set. Also in the PD data was set up to show zero and first order absorption

(2 dosing lines, RATE=0 or RATE=-2, COMP#)

Question -1- Does NONMEM understand that K0 values are to be calculated

from F2.DOSE/D2 or should I have to provide it in the data set ?

Question-2- For ALAG1 and ALAG2 again, does NONMEM understand how to use

them or I have to specify that under $DES using IF (T.LE.ALAG1) etc.?

$MODEL

NCOMP=5

COMP=(DEPOT,DEFDOSE)

COMP=(CENTRAL)

COMP=(TISSUE)

COMP=(RESPONSE)

COMP=(TISSUE)

$PK

CL=CCL

V2=VV2

Q=0.01

V3=2.94

KA=0.004

K0=KK0

TLAG1=1.17

ALAG1=TLAG1

TLAG2=4.7

ALAG2=TLAG1+TLAG2

F1=0.7

F2=0.3

D2=108.96

S2=V2/1000

;PD MODEL

E0= THETA(1)

KIN=(THETA(2))*(EXP(ETA(1)))

KILL=THETA(3)*(EXP(ETA(2)))

K45=THETA(4)

K54=THETA(5)

KOUT=KIN/E0

A_0(4)=E0

A_0(5)=K45*E0/K54

$DES

CONC=A(2)/V2

S=CONC

DADT(1)=-KA*A(1)-K0

DADT(2)=-CL/V2*A(2)+Q/V3*A(3)-Q/V2*A(2)+KA*A(1)+K0

DADT(3)=Q/V2*A(2)-Q/V3*A(3)

DADT(4)= KIN- KOUT*A(4)-(KILL)*S*A(4)-K45*A(4)+K54*A(5)

DADT(5)=K45*A(4)-K54*A(5)

$ERROR

EFF=LOG(A(4))

IPRED=EFF

Y=EFF+ERR(1)

Regards

Neil

--

Indranil Bhattacharya

Received on Wed Feb 10 2010 - 00:04:48 EST

Date: Wed, 10 Feb 2010 00:04:48 -0500

Hi, I have a question regarding how NONMEM reads the code when doing a

sequential PK/PD run.

I fit the PK data (extravascular admin) using a KOKA model with sequential

absorption. The data was based described by this sequential model where K0

process starts after Ka. To fit the data I used ADVAN4 TRANS4 (2 COMP

model).

Now the next step is to fit the PD data and here is where I am confused.

For the PK parameters I designate them under $PK as shown in the code

provided. CL and V2 had individual values which were included in the data

set. Also in the PD data was set up to show zero and first order absorption

(2 dosing lines, RATE=0 or RATE=-2, COMP#)

Question -1- Does NONMEM understand that K0 values are to be calculated

from F2.DOSE/D2 or should I have to provide it in the data set ?

Question-2- For ALAG1 and ALAG2 again, does NONMEM understand how to use

them or I have to specify that under $DES using IF (T.LE.ALAG1) etc.?

$MODEL

NCOMP=5

COMP=(DEPOT,DEFDOSE)

COMP=(CENTRAL)

COMP=(TISSUE)

COMP=(RESPONSE)

COMP=(TISSUE)

$PK

CL=CCL

V2=VV2

Q=0.01

V3=2.94

KA=0.004

K0=KK0

TLAG1=1.17

ALAG1=TLAG1

TLAG2=4.7

ALAG2=TLAG1+TLAG2

F1=0.7

F2=0.3

D2=108.96

S2=V2/1000

;PD MODEL

E0= THETA(1)

KIN=(THETA(2))*(EXP(ETA(1)))

KILL=THETA(3)*(EXP(ETA(2)))

K45=THETA(4)

K54=THETA(5)

KOUT=KIN/E0

A_0(4)=E0

A_0(5)=K45*E0/K54

$DES

CONC=A(2)/V2

S=CONC

DADT(1)=-KA*A(1)-K0

DADT(2)=-CL/V2*A(2)+Q/V3*A(3)-Q/V2*A(2)+KA*A(1)+K0

DADT(3)=Q/V2*A(2)-Q/V3*A(3)

DADT(4)= KIN- KOUT*A(4)-(KILL)*S*A(4)-K45*A(4)+K54*A(5)

DADT(5)=K45*A(4)-K54*A(5)

$ERROR

EFF=LOG(A(4))

IPRED=EFF

Y=EFF+ERR(1)

Regards

Neil

--

Indranil Bhattacharya

Received on Wed Feb 10 2010 - 00:04:48 EST