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taresh41 ☆ Mumbai, 2009-07-20 11:27 (6181 d 02:48 ago) Posting: # 3970 Views: 12,936 |
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Dear All, I have a query regarding sampling time points selection in Bioequivalence studies. e.g.: In case of a drug having tmax = 1.50 to 3.00 hours and Half life around 12 hours, considering the tmax and half life from literature and all other pharmacokinetic parameters the total no. of time points are 22 (sampling up to 48.00 hours). My query is,
— Thanks & Regards, Taresh |
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SDavis ★★  UK, 2009-07-23 11:26 (6178 d 02:48 ago) @ taresh41 Posting: # 3981 Views: 10,505 |
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Dear Taresh, There are many people with more experience of your problem on this board however as it's been quiet I will make a couple of suggestions. The best way to assess the impact of sampling time point selection is to Simulate the trial with different schedules. If you overlay the time-conc plots you will see how Cmax, Tmax & AUC can be affected very easily. I would also review the partial derivative plots for each parameter. Furthermore you can use diagnostic parameters e.g. VIF (Variance Inflation Factor - available in WinNonlin etc.) to assess 'objectively' the better schedule to best estimate your parameters of interest since there will always be a compromise. I can suggest a free webinar that discuss some of the problems so might be useful to you as background; "Critical Path Approach for Development of Generic Products" During this presentation some suggestions are made that maybe useful for you to bear in mind; Absorption phase should include 3-5 sampling time points Cmax region should include 4-8 sampling time points (remember Cmax/Tmax is often the most variable and easy to 'miss') Distribution and Elimination phases should include 4-10 sampling time points If you take the maximum of all of these you have 23 timepoints; generally I would expect some trade-off but overall I would aim that the length of sampling schedule should be at least 4-5 half-life of drug to accurately assess total AUC (so AUClast is >80% AUCinf). Simon. — Simon Senior Scientific Trainer, Certara™ [link=https://www.youtube.com/watch?v=xX-yCO5Rzag[/link] https://www.certarauniversity.com/dashboard https://support.certara.com/forums/ |
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taresh41 ☆ Mumbai, 2009-08-21 09:57 (6149 d 04:17 ago) @ SDavis Posting: # 4083 Views: 10,096 |
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Dear Simon, Thanks for providing the useful information. I would like to ask one more question. For long half life drugs there would be a large number of sampling time points. This increase in sampling time points may increase the blood loss too. USFDA mentions truncated AUC method (i.e. sampling till 72 hours) in such cases. which is generally applied for long half life drugs. Is this truncated AUC method used for ethical reasons (i.e to decrease blood loss)? Does the truncation to 72 hours affect the Plasma Concentration - Time profile of the drug? (As the sampling time points are decreased at the elimination phase) — Thanks & Regards, Taresh |
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Helmut ★★★  Vienna, Austria, 2009-08-21 15:59 (6148 d 22:16 ago) @ taresh41 Posting: # 4087 Views: 10,017 |
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Dear Taresh, sorry for cutting in. ❝ USFDA mentions truncated AUC method (i.e. sampling till 72 hours) in such ❝ cases. Not only USFDA, but the majority of other countries as well. ❝ Is this truncated AUC method used for ethical reasons (i.e to decrease ❝ blood loss)? No. Blood sampling for the later part of the profile of long-half-life drugs commonly is performed in an outpatient manner. If you don't sample at late time points you increase compliance. Volunteers don't have to return to the clinical site frequently and you don't have to worry about lost samples (subject did not return for whatsoever reason). ❝ Does the truncation to 72 hours affect the Plasma Concentration - Time ❝ profile of the drug? How could it? The profile will be unaffected, even not harvesting a single sample! OK, this is a philosophical question reminding me on Schrödinger's Cat, or "Are the stars 'there', even if we don't watch the sky?" Truncation should not be seen as a measure to reduce the number of sampling points. Invest your money in sampling more frequently around tmax - that's the most important part of the profile when it comes to variability. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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taresh41 ☆ Mumbai, 2009-08-24 07:41 (6146 d 06:33 ago) @ Helmut Posting: # 4098 Views: 9,891 |
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Dear Helmut, Thanks for providing the information. — Thanks & Regards, Taresh |
Ing. Helmut Schütz