Bioequivalence and Bioavailability Forum

OT: keep TTT! [PK / PD]

posted by Helmut  – Vienna, Austria, 2013-07-22 16:21 (4369 d 21:35 ago) – Posting: # 11031
Views: 22,190

Dear Yung-jin,

❝ […] I just wondered why you did not respond at that moment.

I was giving a workshop and had limited spare time…

❝ As illustrated, TTT rule may cause extreme bias for λz estimation when the study drug exhibits more than one-compartment PK model, i.e., when it has more than one exponential terms mathematically.

Yes. But still slightly better than R²_adj alone – the only one available in commercial software.

❝ Should I consider to remove TTT from bear first since it is a model-dependent approach?

Please no! Contrary to R²_adj TTT is based on PK-grounds. I would not call it model-dependent. OK, it is based on a one-compartment model but the estimation of λ_z is within the boundaries of NCA, IMHO. For multiple distribution / elimination phases it is the responsibility of the user to select the last loglinear phase visually.

❝ And then we can add it back again when we have clear picture about it.

I think that you should keep it. If we find a reasonable automatic method for >1 compartment you can add it.

Anyhow, I’m not overly optimistic yet – especially if at least one of the following conditions applies:

• Noisy data.
  
• Limited samples, especially in the area of the ‘breakpoint’.
  
• No pronounced difference in rate constants (rule of thumb: ratios ≤5 are difficult to detect).
  
• Large differences in volumes of distribution. Might be only of theoretical interest because one of the phases will not be apparent unless the analytical method is very sensitive.

---

I started a new thread over there.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• 1 compartment model with lag time jag009 2013-07-17 15:58 
  • 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 bear yjlee168 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