Bioequivalence and Bioavailability Forum • OT: TTT in bear

OT: TTT in bear [PK / PD]

posted by yjlee168 – Kaohsiung, Taiwan, 2013-07-19 00:17 (3927 d 03:46 ago) – Posting: # 11024
Views: 21,133

Dear Helmut,

Yes, as I can remember, after we announced bear v1.0.0 on 2008 at this Forum, we took most advices from colleagues of this Forum to improve bear. Adding different algos (such as ARS, TTT, AIC and combo) to estimate λ_z was one of major tasks at that time. When finishing this part, we did some research trying to figure out if different algo really made differences. Basically, we got similar results as you did: no differences could be found with AUC_0-∞, but λ_z and AUC_0-t (AUC from time zero to the last measurable conc.) could be significantly different. We did not publish the results either. I think it mostly can be due to that the extrapolated AUC (AUC_t-∞) is only 10-20% of AUC_0-∞, or even less. Thus it may not have significant impact on AUC_0-∞. I know some countries even do not include AUC_0-∞ as pivotal BE parameters. So I very agree with what you got from comparing different algos for λ_z estimation. However, we did learn a lots from adding these algos into bear.

❝ Incidentally I met one of the authors of the TTT-paper (Christian Scheerans) last month. He knew that you have implemented the method in bear after our discussions in the forum. He was very happy about that. :-D [...]

Thank you and Christian.

❝ After some discussion with Christian we are considering to extend the method for multicompartment profiles. Hopefully it will not go to the to-do-list and stay there forever…

In this thread, I noticed that Detlew mentioned "TTT rule... only restricted to one-compartment model..." And now you say "... to extend the method for multicompartment profiles..." I cannot quite remember if TTT rule in only restricted form one-compartment model or not. Like like it should be. Question is that we all use NCA to analyze BE data (such as Cmax & AUCs). It raises some questions here.

Does it imply that if we want to choose TTT rule to estimate λ_z we need to prove that the study drugs exhibit (or best fit with) the one-compartment model in the body first?
Is it something related to "the inflection point of the curve" (i.e., the second point; the first is Cmax) in one-compartment model?
Should we put "warning" in bear for this restriction?
Also, if TTT rule is a model-dependent algo for λ_z estimation, is it appropriate to add the algo to the part of NCA?

—
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

Complete thread:

1 compartment model with lag time jag009 2013-07-17 15:58 [PK / PD]
- solve for k01? Helmut 2013-07-17 16:08
  - solve for k01? jag009 2013-07-17 16:19
    - solve for k01? ElMaestro 2013-07-17 17:09
    - no closed form Helmut 2013-07-17 23:01
- 1 compartment model with lag time yjlee168 2013-07-17 20:57
- Package-free solution ElMaestro 2013-07-17 21:53
  - Package-free solution yjlee168 2013-07-17 22:11
    - Package-free solution ElMaestro 2013-07-17 22:27
      - Package-free solution yjlee168 2013-07-17 22:42
  - Package-free solution ElMaestro 2013-07-17 23:21
    - A new R-King was born d_labes 2013-07-18 08:45
      - Brent ElMaestro 2013-07-18 09:07
      - A new R-King was born yjlee168 2013-07-18 10:21
        
        OT: TTT in bear Helmut 2013-07-18 20:28
        
        OT: TTT in bearyjlee168 2013-07-18 22:17
        
        OT: TTT subtleties d_labes 2013-07-19 09:47
        
        OT: TTT subtleties yjlee168 2013-07-20 19:44
        
        OT: beyond TTT? Helmut 2013-07-21 00:08
        
        OT: beyond TTT? yjlee168 2013-07-22 13:45
        
        OT: keep TTT! Helmut 2013-07-22 14:21
        
        OT: keep TTT! yjlee168 2013-07-22 23:42
        
        OT: EOD (here) Helmut 2013-07-23 01:06
    - Package-free solution yjlee168 2013-07-18 10:27
      - Thank you guys! jag009 2013-07-18 16:37
        
        Thank you guys! ElMaestro 2013-07-18 18:57
        
        Thank you guys! jag009 2013-07-19 20:40