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  • [NMusers] Win64
    NONMEM users Has anyone running NONMEM on 64 bit Windows If so how did you install it Which compiler was used Sincerely J Lötsch Prof Dr med Jörn Lötsch pharmazentrum frankfurt ZAFES Institut für Klinische Pharmakologie Johann Wolfgang Goethe Universität

    Original URL path: http://nonmem.org/nonmem/nm/99nov232005.html (2016-04-25)
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  • [NMusers] processor choice
    Tue 22 Nov 2005 08 41 48 0500 for an application to take advangate of a dual core cpu much like pentium4 s hyper threading it needs to be a multithreaded and nonmem is about the furtherest thing from multithreaded i did some runtime comparisons on single cpu P4 systems with HT hyper threading enabled and disable and dual cpu P4 systems with HT disabled HT ing doesn t by you anything when running nonmem other then a longer runtimes when you try to run a job cpu take a job that runs in 40 minutes single cpu with HT disable when HT is enable and 2 identical jobs are run one per virtual cpu the jobs take nearly twice as long though runtime is marginally better with HT then when running 2 jobs when HT is disabled when run on a dual cpu system with HT disabled of the same speed the 2 jobs run in the same time as a single job when HT is disabled i can purchase a machine with dual 3 0GHz Intel Xeon processors for 1779 00 a dual core 3 0GHz intel pentium D runs about 1707 00 or a singe 3 0GHz P4 for around 1550 00 if your goal is the maximize the number of nonmem jobs you can run in the shortest amount of time your better for going with dual processor machines any day my 2 cents Darin Perusich Unix Systems Administrator Cognigen Corp darinper cognigencorp com From mark e sale gsk com Subject Re NMusers processor choice Date Tue 22 Nov 2005 09 14 45 0500 Darin is correct NONMEM is single threaded Even if it were multi threaded it probably couldn t take advantage of hyperthreading as the super scalar architecture of Intel and AMD chips provides

    Original URL path: http://nonmem.org/nonmem/nm/99nov212005.html (2016-04-25)
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  • [NMusers] Distribution of Simulated Cmax
    ibmp osn de Subject Re NMusers Distribution of Simulated Cmax Date Sat 19 Nov 2005 18 58 46 0100 Dear Partha I would start with a bootstrap re sampling of the observed Cmax s of your original study If you generate a few thousand bootstrap pseudo samples of the same sample size as used in your study you should get a good idea which degree of similarity in the distribution of Cmax you would expect from a population PK model As long as you have a reasonable number of subjects in your original study the most adequate population PK model should provide you similar simulated Cmax distributions as the bootstrap pseudo samples from the original study Did you check that the extent of absorption was similar in case you pooled data from more than one study Which between and within subject variability from ANOVA statistics did you get from the Cmax of your original study If you have only a few subjects and a large within subject variability between occasion variability then such a formulation might fail to be bioequivalent to itself in a bioequivalence trial Another idea would be to use a different error model around the expected Cmax region Have not tried this myself but might be worth to try Best regards Juergen Juergen Bulitta M Sc Scientific Employee IBMP Paul Ehrlich Str 19 90562 Nuernberg Heroldsberg Germany From Pravin Jadhav pravinj gmail com Subject Re NMusers Distribution of Simulated Cmax Date Sat 19 Nov 2005 12 55 27 0500 Hi Partha This is a classical simulation problem that we have on a few of occasions You say PPC did not show obvious flaws in the model It would really depend on the metric that was used Please take a look at our publication on the very same

    Original URL path: http://nonmem.org/nonmem/nm/99nov192005.html (2016-04-25)
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  • [NMusers] MIXTURE modeling
    do I identify co variates Same procedure as without MIX only separately for the two subpopulations 3 The objective function went down by 55 14 from the model without covariates and without MIX but the subpopulations do not appear meaningful This applies also to the quite high as compared to the estimate without MIX volume of distribution that does not vary interindividually in one subpopulation How do I deal with this result Thank you in advance for your advice Sincerely J Lötsch Prof Dr med Jörn Lötsch pharmazentrum frankfurt ZAFES Institut für Klinische Pharmakologie Johann Wolfgang Goethe Universität Theodor Stern Kai 7 D 60590 Frankfurt am Main Tel 069 6301 4589 Fax 069 6301 7636 http www klinik uni frankfurt de zpharm klin From Gobburu Jogarao V GOBBURUJ cder fda gov Subject RE NMusers MIXTURE modeling Date Thu 17 Nov 2005 06 17 25 0500 Hello please see my responses below 0 First of all I am not sure what prompted you to apply a mixture model and how rich the data are 1 You do not have to estimate different modes for the two populations for all the parameters You should limit it to the ones that you think are reasonable ie you need some prior expectation eg poor vs fast metabolizers or graphical evidence 2 Covariate selection should be similar with or without MIX However it would be important to explore if one or several of the covariates can explain the mixture 3 Bruce Green and Nick Holford presented some work on using log likelihood ratios to select mixture models at the Annual AAPS meeting last week asymptotic vs empirical via re randomization tests They show that the estimation method FO vs FOCE makes a big difference They may have more to add on this Regarding volume for

    Original URL path: http://nonmem.org/nonmem/nm/99nov172005.html (2016-04-25)
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  • [NMusers] Incorporating duplicate assays
    structure The concept of nested random effects may suite Below is an example of the ERROR block that you can try REPEATED OBS OBS1 0 OBS2 0 OBS3 0 IF OBSN EQ 1 OBS1 1 IF OBSN EQ 2 OBS2 1 IF OBSN EQ 3 OBS3 1 ASSERR OBS1 ERR 1 OBS2 ERR 2 OBS3 ERR 3 Y F 1 ASSERR ERR 4 SIGMA BLOCK 1 1 SIGMA BLOCK 1 SAME SIGMA BLOCK 1 SAME SIGMA 2 Best regards Vladimir Vladimir Piotrovsky Ph D Research Fellow Advanced PK PD Modeling Simulation Clinical Pharmacology and Experimental Medicine Johnson Johnson Pharmaceutical Research Development B 2340 Beerse Belgium From Leonid Gibiansky leonidg metrumrg com Subject Re NMusers Incorporating duplicate assays Date Wed 16 Nov 2005 15 25 21 0500 Hi Paul Technically this is correct I had duplicate measurements in some of the NONMEM runs and there were no complaints from the program concerning the duplicate times For the actual data set residual error consists of the assay error unexplained error I think that the second component is usually larger Repeated measurements at the same point cannot help with that part If you have the same number of measurement for the majority of points you can average before running the model thus creating the new more precise and less variable assay as an average of x number of measurements at each point Thanks Leonid From Hutmacher Matt Matt Hutmacher pfizer com Subject RE NMusers Incorporating duplicate assays Date Wed 16 Nov 2005 15 33 57 0500 Paul and Vladimir Adding in misspecification is a good point to consider Also it should be noted that if the re assay comes from the same sample the experimental unit becomes the blood draw potentially inducing correlation between these observations similar to parent metabolite correlation Thus the L2 data item and a SIGMA block could be evaluated Matt From Piotrovskij Vladimir PRDBE VPIOTROV PRDBE jnj com Subject RE NMusers Incorporating duplicate assays Date Fri 18 Nov 2005 10 14 28 0100 Matt I don t think there is any correlation in the case of duplicated assays In the model Yijk Fij 1 ETAij ETAijk higher ETAij is not necessarily accociated with systematically higher or lower ETAijk I do not see any reason of using L2 data item The situation is completely different compared to the parent metabolite correlation you mention There are here 2 analytes BTW an example of using L2 presented in the NONMEM user guide V includes simultaneous analysis of PK and PD data it is also an example of 2 types of observations that may indeed correlate Best regards Vladimir From Mats Karlsson mats karlsson farmbio uu se Subject RE NMusers Incorporating duplicate assays Date Fri 18 Nov 2005 11 05 49 0100 Hi Vladimir The L2 data item is necessary as the duplicates will share a common residual error due to error in dosing history sampling time model misspecification etc The only way to have two observations share an EPS is by using

    Original URL path: http://nonmem.org/nonmem/nm/99nov162005.html (2016-04-25)
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  • [NMusers] FW: question for absorption modeling
    I enter RATE for the zero order absorption and control file for these 2 situations Can I continue using the library models or do I need to switch to user written subroutines Thanks Ritu Ritu Lal Ph D Sr Director Pharmacokinetics and Drug Metabolism Xenoport 3410 Central Expressway Santa Clara CA 95051 Phone 408 616 7199 Cell 408 483 3741 Fax 408 616 7212 e mail ritu lal xenoport com From Justin Wilkins justin wilkins farmbio uu se Subject Re NMusers question for absorption modeling Date Mon 07 Nov 2005 10 42 58 0100 Hi there I don t think there ll be any problem using the library routines for this Specifying RATE 2 indicates that the durations as opposed to rates of zero order bolus doses will be calculated by PK For ADVAN2 TRANS2 you might use a data file structure similar to the following example ID RATE TIME DV MDV AMT EVID 1 2 0 0 1 600 1 1 0 1 55 3 98 0 0 0 1 0 3 13 4 32 0 0 0 1 0 4 78 3 22 0 0 0 2 2 0 0 1 600 1 2 0 3 18 0

    Original URL path: http://nonmem.org/nonmem/nm/99nov042005.html (2016-04-25)
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  • [NMusers] DOS emulation window issue
    mouse button and drag Look at the title bar when this happens you ll see select MS DOS hit any key and the select goes away and the file is open again The annoying thing is that NONMEM doesn t freeze until it gets to a point where it tries to output to the console then finds that the file is locked and waits until it is unlocked No specific cure except to make sure you hit the ENTER key before you go home at night or at least look at the title bar Or you could edit the BLKDAT for file and get rid of the output to the console haven t tried that but it should work Mark Sale M D Global Director Research Modeling and Simulation GlaxoSmithKline 919 483 1808 Mobile 919 522 6668 From Peterson Mark markp amgen com Subject RE NMusers DOS emulation window issue Date Wed 2 Nov 2005 13 32 41 0800 Mark Thank you for this explanation This makes sense All the best Mark Peterson From mark e sale gsk com Subject RE NMusers DOS emulation window issue Date Wed 2 Nov 2005 20 32 27 0500 I see I had a small cerebral eructation it is left mouse button and drag to select text in MS DOS windows not right mouse button Mark Sale M D Global Director Research Modeling and Simulation GlaxoSmithKline 919 483 1808 Mobile 919 522 6668 From Abutarif Malaz malaz abutarif spcorp com Subject RE NMusers DOS emulation window issue Date Thu 3 Nov 2005 17 37 26 0500 Mark This is appreciated For automation of runs I use SPLUS and run NonMem from SPLUS using the dos command Do you know or does anyone know if this is also true in that case Do we need to watch out for this and how from within SPLUS I will have to choose the option multi F to be able to automate multiple runs and the output is inside the SPLUS script window i e there is no title for a Dos window Thanks in advance Malaz From Piotrovskij Vladimir PRDBE VPIOTROV PRDBE jnj com Subject RE NMusers DOS emulation window issue Date Fri 4 Nov 2005 10 03 33 0100 Malaz dos function is deprecated in S PLUS 2000 and higher although still supported I use the function system that is quite flexible The following command system C WINNT SYSTEM32 CMD EXE c start LOW i C nmv run nmfe5 mod txt out txt multi T opens the dos window and sets the priority of the process to low You can use other applications and will observe no delays After NONMEM run stops the dos window remains open allowing you to examine NONMEM messages if any Another command ystem c nmv run nmfe5 bat mod txt out txt multi T creates the nonmem process with high priority and after the run stops closes the dos window It is convenient for multiple runs like bootstrapping The argument multi

    Original URL path: http://nonmem.org/nonmem/nm/99nov022005.html (2016-04-25)
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  • [NMusers] the number of records in one individual
    DATA RECS IN BUFFER 1 IS LESS THAN NO OF DATA RECS IN INDIVIDUAL REC NO 1 IN INDIVIDUAL REC ORDERING If I reduce the records to about 800 it runs fine Is there like a limit on the buffer 1 size in NONMEM Thanks Kai Wu Department of Pharmaceutics University of Florida Gainesville Fl Office phone 352 846 2730 From kai wu kaiwu77 yahoo com Subject RE NMusers the

    Original URL path: http://nonmem.org/nonmem/nm/99nov012005.html (2016-04-25)
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