RE: Predict AUC based on trough concentrations

From: Yaming Hang Date: February 18, 2010 technical Source: mail-archive.com
Dear All, I'm grateful for the many responses that you posted to my question regarding AUC prediction based on a few trough concentrations. My final conclusion on this problem is that it is related to the improper configuration of the SIZES file. Before this large scale exercise, I did some thing similar with a much small trial (12 subjects with less than 30 time points each) on my laptop, no problem with that one at all. The initial error message with the large scale problem (run on laptop) is about the MAXID parameter in SIZES file. Although I've increased the value of MAXID and NO parameters and recompiled, there was still error message. I was told by a colleague that if several other parameters are not changed accordingly, the issue is not completely solved. So eventually I run the NONMEM control file on Unix system where much larger MAXID and NO are allowed, and it worked. Thanks for your suggestions of adding an AUC compartment, this is certainly something new I learned. Kind regards, Yaming
Quoted reply history
-----Original Message----- From: Johan Wallin [mailto:[email protected]] Sent: Thursday, February 18, 2010 9:23 AM To: Hang, Yaming Subject: Re: [NMusers] Predict AUC based on trough concentrations Yaming, Maybe I misunderstood what you were trying to do here. As I interpret you were not simulating and reestimating, but rather just want to calculate AUC:s based on the EBE parameters from sparse sampling? An easier way would be to simply calculate AUC in your original run, i.e. tabulating AUCi based on the CLi. That would eliminate the need for this second run, and resetting the sizes. /Johan Johan WALLIN PhD Research Scientist PK/PD/TS Lilly UK (Embedded image moved to file: Erl Wood Manor pic26308.gif) Windlesham, Surrey, GU20 6PH UNITED KINGDOM Tel: +44 1276 483273 Fax: +44 1276 484367 www.lilly.co.uk CONFIDENTIALITY NOTICE: This e-mail message from Lilly UK (including all attachments) is for the sole use of the intended recipient(s) and may contain confidential and privileged information. Any unauthorized review, use, disclosure, copying or distribution is strictly prohibited. If you are not the intended recipient, please contact the sender by reply e-mail and destroy all copies of the original message. E-mail is susceptible to data corruption, interception, unauthorized amendment, tampering and viruses, and we only send and receive e-mails on the basis that we are not liable for any such corruption, interception, amendment, tampering or viruses or any consequences thereof. Eli Lilly and Company Limited, a company incorporated in England under company registration number 284 385 and having its registered office at Lilly House, Priestley Road, Basingstoke, Hampshire RG24 9NL "Hang, Yaming" <yaming_h...@merc k.com> To Sent by: <[email protected]> owner-nmus...@glo cc bomaxnm.com Subject [NMusers] Predict AUC based on 17/02/2010 18:22 trough concentrations Dear NONMEM Users, I have a study where I'd like to predict AUC based on 2~3 trough concentrations. There are about 500 subjects and I intend to predict drug concentration for 560 time points for each subject (10 time points/day * 56 days). The EBE for model parameters for each individual have been generated and they will be fed into NONMEM for calculation of drug concentrations. The following is the relevant NONMEM code: $INPUT ID DOSE=DROP DAYN TIME AMT DV EVID MDV ADDL II CONC CLI V2I Q3I V3I Q4I V4I KAI F1I ALGI $SUBROUTINES ADVAN12 TRANS4 $PK CL=CLI V2=V2I KA=KAI F1=F1I Q3=Q3I V3=V3I Q4=Q4I V4=V4I ALAG1=ALGI S2=V2I*624.709/1E6 $ERROR IPRED=F Y=F $SIMULATION (26730517) ONLYSIMULATION SUBPROBLEMS=1 But I get error message like 0WARNING: MAXIMUM NUMBER OF THETA'S PLUS VARIANCE COMPONENTS EXCEEDS MAXIMUM NUMBER OF PARAMETERS THAT CAN BE ESTIMATED. SEE INSTALLATION GUIDE I've increased LTH to 60 in file SIZES, LVR has a value of 30, but still encounter this error message. Does anybody have done similar thing in the past? What's likely to be the true issue here? Your suggestion will be greatly appreciated. Yaming Notice: This e-mail message, together with any attachments, contains information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA 08889), and/or its affiliates Direct contact information for affiliates is available at http://www.merck.com/contact/contacts.html) that may be confidential, proprietary copyrighted and/or legally privileged. It is intended solely for the use of the individual or entity named on this message. If you are not the intended recipient, and have received this message in error, please notify us immediately by reply e-mail and then delete it from your system. Notice: This e-mail message, together with any attachments, contains information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA 08889), and/or its affiliates Direct contact information for affiliates is available at http://www.merck.com/contact/contacts.html) that may be confidential, proprietary copyrighted and/or legally privileged. It is intended solely for the use of the individual or entity named on this message. If you are not the intended recipient, and have received this message in error, please notify us immediately by reply e-mail and then delete it from your system.
Feb 17, 2010 Yaming Hang Predict AUC based on trough concentrations
Feb 17, 2010 Sam Liao RE: Predict AUC based on trough concentrations
Feb 18, 2010 Leonid Gibiansky Re: Predict AUC based on trough concentrations
Feb 18, 2010 Yaming Hang RE: Predict AUC based on trough concentrations