Bioequivalence and Bioavailability Forum

Cτ predictive of Cmin [General Sta­tis­tics]

posted by Helmut  – Vienna, Austria, 2013-11-30 18:25 (4218 d 14:57 ago) – Posting: # 11993
Views: 15,041

Hi Luv,

❝ Yes, the ratio's were on lower side.The T/R ratio was ~87 for Cmin (lower CI was 76.8) and Same was the case for AUCtss (~89 with range of 78-99).

❝

❝ When we were trying to understand the reason of failure, one thing that draw our attention was the lower AUC values in SD. And this lower accumulations might have lead to the lower Cmin and AUCtss.

I tried to simulate some stuff matching your SD results (AUC 89%, C_max 97%) and MD (AUC 89%). The best I could get (assuming identical t_1/2) was F 79.44% combined with faster absorption. Example:



    Test    Reference
F%  79.44   100.00   
ka   0.3466   0.4578

               %T/R   
             SD     MD
AUCt        90.1       
AUC∞        89.0       
AUCτ               89.1
Cmax        97.0   95.1
Cmax/AUC∞  108.9       
Cmax/AUCτ         107.7
Cτ          79.7       
Cmin               79.7

The faster absorption of the test counteracts its lower bioavailability (C_max-ratio > AUC-ratio). Since C_max is influenced by extent of absorption, C_max/AUC tells a better story – although k_a of the test is actually by 32% faster. C_τ is predictive of C_min. However, if I want to get your 87% I would have to assume different half-lives. Were you close to flip-flop PK? Did you have any hints of nonlinear PK?

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


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Complete thread:

• Simulation of data to predict Steady state cakhatri 2013-11-24 10:13 [General Sta­tis­tics] 
  • Nonparametric superposition Helmut 2013-11-24 14:30
    • Nonparametric superposition jag009 2013-11-24 23:13
      • Nonlinear nightmare Helmut 2013-11-25 02:56
        • Nonlinear nightmare jag009 2013-11-25 17:43
          • Nonlinear nightmare Helmut 2013-11-26 14:32
            • Nonlinear nightmare jag009 2013-11-26 16:00
              • OT: Vienna Helmut 2013-11-26 16:27
                • OT: Vienna jag009 2013-11-26 17:29
                  • OT: Vienna Helmut 2013-11-27 13:04
    • Conc at dosing interval jag009 2013-11-25 17:48
      • Conc at dosing interval Helmut 2013-11-26 15:01
        • Conc at dosing interval jag009 2013-11-26 17:31
          • Conc at dosing interval Helmut 2013-11-27 13:10
            • Conc at dosing interval jag009 2013-11-27 20:00
            • Passing SD and Failing MD luvblooms 2013-11-28 09:19
              • Passing SD and Failing MD Helmut 2013-11-29 17:29
                • Passing SD and Failing MD luvblooms 2013-11-29 18:57
                  • Cτ predictive of CminHelmut 2013-11-30 17:25