[NMusers] Implementation of NM to analyze in-vitro data on drug synergy

Dear NMUSERS, I was wondering if anyone on this list has experience implementing analysis of in-vitro data on drug synergy (combination of two anticancer drugs in different concentrations) with the help of NONMEM, e.g. by the method of Chou and Talalay (Cancer Research 70: 440-446 (2010)) or an

RE: [NMusers] Weighting observations

Hi Robert, Just wondering: what drug are you modeling? A beta-blocker? An ACE inhibitor? My gut feeling tells me you should also incorporate some feedback between drug effects like blood pressure, heart rate and urine output with these drugs based on their mode of action instead of considering

[NMusers] RE: integrated parent-metabolite PK model from sequential iv and oral doses of parent drug

Dear Kok-Yong Seng, Is the drug undergoing presystemic metabolism after oral administration? This might explain some differences in metabolic rate constants before and after oral administration. If your drug undergoes presystemic metabolism, metabolite concentrations may appear earlier in the s

RE: [NMusers] Transit Absorption Model in NONMEM

Hi Xinting , You might want to check out the PDF of the presentation of Justin Wilkins at the PAGE in 2005: http://www.page-meeting.org/?abstract=769 By the way, in my experience this model does not really outperform a little more simple method with a chain of transition/absorption compartments

RE: [NMusers] Reporting and handling values below the limit of quantification

Hi Paolo, I've been recently thinking about this matter as well. I ultimately decided to include all concentration data below the LOQ, if in the chromatogram they had a signal to noise ratio of >5 (compared with blank plasma) and to estimate the additive component of the residual error whenever

RE: [NMusers] Reporting and handling values below the limit of quantification

Hi Paolo, Considering 2A: The residual error model always should already account for a possible larger residual error at lower concentrations. I think a combined proportional and additive error model willfor this. If an additive component can't be estimated, my gut feeling tells me fixing the

RE: [NMusers] The theory of relativity for CL and V...

Dear Paolo, The reduced bioavailability is most likely a result of increased, however variable, pre-systemic metabolism which also correlates with systemic clearance. Have you tried linking these together in your model, e.g. with a well-stirred liver model (e.g. Gordi et al Br J Clin Pharmacol. 20

[NMusers] OS X 10.7 to 10.8 update with NONMEM/PIRANA

Hi all, I updated from OS X 10.7 to 10.8 yesterday and found my Nonmem/Pirana installation not working anymore. Just wanted to share my experience getting Nonmem 7.2 and Pirana 2.5.0 to work again. 1. OS X no longer supports X11, required for pirana. One should therefore download XQuartz from x

RE: [NMusers] Modeling variability in absorption and clearance (Auto induction)

Dear Shankar Lanke, you can try modeling variable absorption with a chain of transit compartments and estimating the mean absorption and to account for interoccasion variability in relative oral bioavailability (e.g. F1=1*EXP(ETA(1)). Other things that you should account for with efavirenz in

RE: [NMusers] Installation of NM7.2 on OSX lion for dummies.

Dear all, Thanks for the many suggestions getting this to work. I got NONMEM installed on OSX 10.7 lion as follows: 1. Enabled root access as described here: http://www.macosliontips.com/tips/enable-root-account-in-mac-os-x-lion.h tml 2. Created the folders /opt and /opt/nm7.2 manually 3. Inst

RE: [NMusers] Autoinduction model - An increased clearance(day 1- 14)

Dear Shankar, As I read it, if your autoinduction is complete after 14 days, you do not really have the data describing the autoinduction process, except for a single trough sample, which is probably not enough considering the inter-occasion variability in F and probably only a marginal or absent

RE: [NMusers] Autoinduction model - An increased clearance(day 1- 14)

Dear Shankar, How rich is your dataset? In other words: do you have enough data troughout the induction period to estimate the lagtime? You could, for example try to fix the lagtime to a reasonable time and estimate the inter-individual variability. Another way of estimating the autoniduction is

RE: [NMusers] change calculation of WRES?

Dear Nele, Couldn't this be solved by simply turning on a flag after a certain time and estimate a seperate residual error when this flag is turned on? Ofcourse you can also code this flag in your dataset. Rob Van: owner-nmus...@globomaxnm.com [mailt