time-dependent clearance [Tips / Tricks]

posted by yjlee168 Homepage – Kaohsiung, Taiwan, 2010-11-09 21:16 (4887 d 16:04 ago) – Posting: # 6126
Views: 17,743

Dear Luvblooms,

I guess you're talking about time-dependent clearance here.

❝ But, even the tissue where it has been distributed keeps on proliferating or growing thus increasing the number of cells available for metabolism or in other term with increase in the number of cell, the metabolic capability increases thus that may lead to increase metabolism of the drug in that specific region or tissue.


❝ My question is that

❝ 1. Is there will be any effect on the PD out come because of the increased metabolism/ increased metabolic activity of the tissue where the drug is distributed or it is simply controlled by the systemic clearance?


Yes and no. It depends on the changes of clearance (Cl). However, you may need to know when Cl is going to change (its starting time and stopping time) first. Of course, you can have as many as Cls you want, only if you need to know each Cl's starting time and stopping time to switch to different Cl. That's the difficult part. However, you figure it out from your data by plotting all data with 'Conc. vs. Time' first; and make your guess. It may take you some time to get good guess (trial-and-error).

❝ 2. Is there any PK PD model is available for the same?


Not totally the same but should have a lot of similar PK/PD models. You can look for Pubmed with keyword "time-dependent clearance" or google it.

❝ 3. If no PK PD model available, what approaches one should try for to generate one.


❝ I hope someone at the forum will help me out with this as I am stuck and not finding any way out.


I think you may need to create this model yourself to fit your data (needs). I would suggest that you can try ADAPT v5 (a fortran compiler required, freeware), Boomer (no compiler required, freeware), or Winnonlin (commercial), SAAM-II (commercial). Hope this can help.

All the best,
-- Yung-jin Lee
bear v2.9.1:- created by Hsin-ya Lee & Yung-jin Lee
Kaohsiung, Taiwan https://www.pkpd168.com/bear
Download link (updated) -> here

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