From: Steve Troy <*stroy*>

Date: Wed, 11 Apr 2007 10:02:03 -0400

Dear Abduljalil,

I am not an expert on using the Weibull distribution for drug

absorption, but I suspect that the value of TIME in the equation for

DADT(1) should represent the elapsed time since the most recent dose.

For example, if dosing occurs at 0, 24, and 48 hours, then the

observation at 25 hours after the start of the study (ie, 1 hour after

the most recent dose) should use TIME=1 hour in the equation for

DADT(1). However, I suspect that TIME=25 hours is being used in the

current problem.

Good luck,

Steve

-----Original Message-----

From: owner-nmusers

On Behalf Of Khaled Mohammed Abduljalil

Sent: Wednesday, April 11, 2007 9:15 AM

To: nmusers

Subject: [NMusers] Weibull distribution

Dear NONMEM users,

I have tried to study the pk profiles of a drug after

multiple oral dosage regimen of 500mg every 12hr. The

estimation process was well performed with the first dose

(only) using Weibull function. but if i apply the same

control file to the whole data (ie, single dose and

multiple doses), it does not work any more. I can not

detect my error. Could any one tell me where is it?

neither first order nor Mich.-Menten models fitted the

data like weibull model.

thank you very much in advance for your response.

sincerely yours

Abduljalil

$SUBROUTINES ADVAN6 TRANS1 TOL=3

$MODEL

COMP=(DEPOT,DEFDOSE)

COMP=(CENTRAL,DEFOBS)

$PK

CL=THETA(1)*EXP(ETA(1))

V=THETA(2)*EXP(ETA(2))

BETA=THETA(3)*EXP(ETA(3))

ALPHA=THETA(4)*EXP(ETA(4))

K=CL/V

S1=1

S2=V

$ERROR

DEL=0

IF(F.EQ.0) DEL=0.001

W=F

IPRED=F

IRES=DV-IPRED

IWRES=IRES/(W+DEL)

Y=F+EPS(1)

$DES

DADT(1)=-A(1)*(BETA/ALPHA)*((TIME/ALPHA)**(BETA-1))*EXP(-(TIME/ALPHA)**=

B

ETA)

DADT(2)=-DADT(1)-A(2)*K

$THETA

(0.01,17,80);

(10,115,900);

(0.1,2.2,30)

(0.1,2.6,30)

(0.001,2)

(0.001,1)

$OMEGA

0.1 0.2 0.08 0.2

$SIGMA

0.2

$EST METHOD=1 INTER PRINT=5 NOABORT MAXEVAL=9999

************************************************************

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contain confidential or privileged information. If you are

not the intended recipient, you are hereby notified that

any use, distribution, disclosure or copying of this

message, any attachment or the information contained

therein is strictly prohibited. If you have received this

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************************************************************

Received on Wed Apr 11 2007 - 10:02:03 EDT

Date: Wed, 11 Apr 2007 10:02:03 -0400

Dear Abduljalil,

I am not an expert on using the Weibull distribution for drug

absorption, but I suspect that the value of TIME in the equation for

DADT(1) should represent the elapsed time since the most recent dose.

For example, if dosing occurs at 0, 24, and 48 hours, then the

observation at 25 hours after the start of the study (ie, 1 hour after

the most recent dose) should use TIME=1 hour in the equation for

DADT(1). However, I suspect that TIME=25 hours is being used in the

current problem.

Good luck,

Steve

-----Original Message-----

From: owner-nmusers

On Behalf Of Khaled Mohammed Abduljalil

Sent: Wednesday, April 11, 2007 9:15 AM

To: nmusers

Subject: [NMusers] Weibull distribution

Dear NONMEM users,

I have tried to study the pk profiles of a drug after

multiple oral dosage regimen of 500mg every 12hr. The

estimation process was well performed with the first dose

(only) using Weibull function. but if i apply the same

control file to the whole data (ie, single dose and

multiple doses), it does not work any more. I can not

detect my error. Could any one tell me where is it?

neither first order nor Mich.-Menten models fitted the

data like weibull model.

thank you very much in advance for your response.

sincerely yours

Abduljalil

$SUBROUTINES ADVAN6 TRANS1 TOL=3

$MODEL

COMP=(DEPOT,DEFDOSE)

COMP=(CENTRAL,DEFOBS)

$PK

CL=THETA(1)*EXP(ETA(1))

V=THETA(2)*EXP(ETA(2))

BETA=THETA(3)*EXP(ETA(3))

ALPHA=THETA(4)*EXP(ETA(4))

K=CL/V

S1=1

S2=V

$ERROR

DEL=0

IF(F.EQ.0) DEL=0.001

W=F

IPRED=F

IRES=DV-IPRED

IWRES=IRES/(W+DEL)

Y=F+EPS(1)

$DES

DADT(1)=-A(1)*(BETA/ALPHA)*((TIME/ALPHA)**(BETA-1))*EXP(-(TIME/ALPHA)**=

B

ETA)

DADT(2)=-DADT(1)-A(2)*K

$THETA

(0.01,17,80);

(10,115,900);

(0.1,2.2,30)

(0.1,2.6,30)

(0.001,2)

(0.001,1)

$OMEGA

0.1 0.2 0.08 0.2

$SIGMA

0.2

$EST METHOD=1 INTER PRINT=5 NOABORT MAXEVAL=9999

************************************************************

The contents of this message are intended only for the use

of the individual to which they are addressed and may

contain confidential or privileged information. If you are

not the intended recipient, you are hereby notified that

any use, distribution, disclosure or copying of this

message, any attachment or the information contained

therein is strictly prohibited. If you have received this

transmission in error, please notify the original sender

immediately and delete all copies of this message, along

with any attachments. Thank you.

************************************************************

Received on Wed Apr 11 2007 - 10:02:03 EDT