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manojkarwa ☆  New Delhi, 2008-04-01 15:49 (6246 d 04:30 ago) Posting: # 1739 Views: 6,647 |
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Dear Sir, I have calculated Pk parameter by NCA modeling by using WinNonLin software but ratio of AUC0-inf to AUC0-t was less than 0.8 in some cases and Rsq is also less than 0.8 in those cases. This is when software automatically select the time points for the calculation of elimination rate constant (Lamda_z). After that i selected time points manually for calculation of Lamda_z in such a way that Rsq valule comes atleast above 0.8. Now ratio of AUC0-inf to AUC0-t is improved and CV% for AUC0-inf is reduced etc. These time points were selected after the Cmax and above the LOQ. But i don't know that is this right way to calculate these parameter. Is there any suitable technical or regulatory guideline for calculating these parameter (or selection of time points for Lamda_z calculation). Best Regards |
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manojkarwa ☆ New Delhi, 2008-04-02 11:15 (6245 d 09:04 ago) @ manojkarwa Posting: # 1744 Views: 5,331 |
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Dear Sir, I received below mentioned reply in my mail but it is not reflecting in the forum. I don't know how? ---- insert from mail ----Dear Manoj, ❝ ...i selected time points manually for calculation of ❝ Lamda_z in such a way that Rsq value comes at least above 0.8 Maybe it only comes from the wording you use, but I don't like the sound of that. And that's exactly where you may run into trouble with regulators, especially in the case of an inspection  .When BE guidelines tell you that AUC0-t should cover at least 80 % of AUC0-inf, it means that you should design your trial in such a way that it will be at least 80 % (adapting sampling duration and LLOQ); not that you should cook your data till it gets to at least 80 %, selecting points that would belong to the ditribution phase and not to the terminal elimination phase in order to reduce t1/2 and % extrapolation. Have a look at this thread for previous discussions on half life calculations. Regards Ohlbe ---- end insert ----Answering to above mentioned reply I understand that it might not be the right way but software may also select the wrong time points for calculation and that might be the reason for erratic results i am getting. And There may be some logic behind providing such feature (manual selection of time point for calculation of elimination rate constant)in the software. So again my question is that how to decide those time points. I wanted to further add some information about the study i conducted. I have measured the concentration up to 48 hr but in most of the subjects we were able to detect the concentration upto 10 hr above LOQ (0.3 ug/ml) and after 6 hr concentration is less than 1 ug/ml in most of the subject. But sometimes some subject have plasma concentration above LOQ after 10 hr also. That is briefly about the pharmacokinetic of drug. Let me know if you need further any information about the kinetic of drug. -- Edit: Broken links removed, order altered for clarity. [Helmut] |
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Ohlbe ★★★ France, 2008-04-02 12:10 (6245 d 08:09 ago) @ manojkarwa Posting: # 1746 Views: 5,213 |
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Dear Manoj, ❝ I received below mentioned reply in my mail but it is not reflecting in the forum. I don't know how? I deleted my message from the forum almost immediately after posting it as I realised I had misunderstood your message. The consequence of the changes in the selection of the data points was an improvement in the R2 result. There was additionally an improvement in the % extrapolation for some subjects, but I read your message too fast and mixed up the two things. Sorry for this. Have a look at this thread for previous discussions on selection of the points for calculation of t1/2 and use of R2. Regards Ohlbe |
Ing. Helmut Schütz