From: Nick Holford <*n.holford*>

Date: Thu, 12 Apr 2007 02:41:09 +1200

Steve makes a good point. You should be using the special variable T in $DES not TIME. T is the instantaneous value of time used by the DE solver. TIME is the time of the current record which the DE solver is attempting to move towards to find a solution.

Try this for DADT(1):

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

Nick

Steve Troy wrote:

*>
*

*> 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.
*

*> ************************************************************
*

--

Nick Holford, Dept Pharmacology & Clinical Pharmacology

University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand

email:n.holford

http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

Received on Wed Apr 11 2007 - 10:41:09 EDT

Date: Thu, 12 Apr 2007 02:41:09 +1200

Steve makes a good point. You should be using the special variable T in $DES not TIME. T is the instantaneous value of time used by the DE solver. TIME is the time of the current record which the DE solver is attempting to move towards to find a solution.

Try this for DADT(1):

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

Nick

Steve Troy wrote:

--

Nick Holford, Dept Pharmacology & Clinical Pharmacology

University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand

email:n.holford

http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

Received on Wed Apr 11 2007 - 10:41:09 EDT