Bioequivalence and Bioavailability Forum • Urban legend?

Urban legend? [Regulatives / Guidelines]

posted by d_labes – Berlin, Germany, 2008-11-24 16:06 (6425 d 23:39 ago) – Posting: # 2790
Views: 27,319

Dear Helmut!

❝ ❝ But you can do it on your own: Fire up some PK software (even M$-Excel would do the job) - define parameters of two hypothetical formulations in such a way that C_max is let's say 10% apart - go into steady state - the difference should be smaller.

❝

❝ Really? Or just an Urban legend of the pharmacokinetolophystic (© ElMaestro) type?

Self-doubts are the essence of real scientific work! :-D

❝ ... ratio stays the same. Am I missing something?

Try to change not F in the model, but rather the absorption constant k_a. Or both.

Using a one-compartment model and the rate constants

k_e=0.06
k_a(test)=2
k_a(ref)=4

I obtained (F, dose and V_c identical for both formulations)
- single dose Cmax ratio=0.9565
- steady state Cmax ratio=0.9711 (tau=8 h)
(Hope I have implemented the formulas in M$-Excel in a hurry right).

To quote your link to Wikipedia:
"Like all folklore, urban legends are not necessarily false but they are often distorted, exaggerated, or sensationalized over time.." ;-)

.
This one and a half percent increase is not so impressive to me. Me be two-compartment models do it better. Or both changes in F and k_a.

—
Regards,

Detlew

Complete thread:

Critical review of EU BE guideline (Rev.1) Helmut 2008-08-22 14:30
- Critical review of EU BE guideline (Rev.1) d_labes 2008-08-22 15:42
  - Critical review of EU BE guideline (Rev.1) Helmut 2008-08-23 02:02
    - Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 09:14
      - Variations Helmut 2008-08-25 11:06
- Critical review of EU BE guideline (Rev.1) Jaime_R 2008-08-23 16:47
  - Critical review of EU BE guideline (Rev.1) Ravi 2008-08-25 08:19
    - Two Stage Design Helmut 2008-08-25 11:43
      - Two Stage Design JPL 2008-08-28 09:44
        
        Two Stage Design Helmut 2008-08-28 11:50
        
        Two Stage Design d_labes 2008-08-28 12:09
        Sequential Design Helmut 2008-11-05 13:22
  - Critical review of EU BE guideline (Rev.1) banusunman 2008-08-26 16:56
    - Washout Helmut 2008-10-15 16:02
- Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 09:49
  - Critical review of EU BE guideline (Rev.1) Helmut 2008-08-25 12:11
    - Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 13:03
    - Urban legend? Helmut 2008-11-21 16:06
      - Urban legend?d_labes 2008-11-24 15:06
- Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 11:16
- Critical review of EU BE guideline (Rev.1), tmax, MRT, LZ d_labes 2008-08-25 11:32
  - Critical review of EU BE guideline (Rev.1), tmax, MRT, LZ Helmut 2008-08-25 13:10
  - tmax, nonparametrics Helmut 2008-10-13 15:38
    - tmax, nonparametrics d_labes 2008-10-14 08:33
      - tmax, nonparametrics Helmut 2008-10-14 11:29
      - tmax, Canadian approach Helmut 2008-11-21 15:41
        
        tmax, Canadian approach d_labes 2008-11-24 13:53
        
        Early exposure, Canadian approach: GMR only! Helmut 2009-02-08 00:44
        
        Early exposure, Canadian approach: GMR only! d_labes 2009-02-09 08:50
        
        tmax; another example Helmut 2008-12-25 15:59
- Automatic integration janmacek 2008-08-27 12:21
  - Automatic integration Ohlbe 2008-08-27 14:49
    - Manual reintegration! H_Rotter 2008-08-28 11:28
      - Manual reintegration! ElMaestro 2008-08-28 12:44
- Subject accountability, Proc MIXED or equivalent d_labes 2008-09-02 11:13
  - Subject accountability, Proc MIXED or equivalent Ohlbe 2008-09-02 15:20
    - Subject accountability, Proc MIXED or equivalent d_labes 2008-09-02 16:30
- partial AUC, early exposure d_labes 2008-09-03 08:35
- HVDs? Helmut 2008-09-23 12:52
  - HVDs? d_labes 2008-09-23 14:20
  - HVDs? Helmut 2009-01-20 14:33
  - E.g., omeprazole Helmut 2009-03-06 17:21
- BCS-based Biowaiver Helmut 2008-09-25 15:48
  - Dissolution update Helmut 2008-10-13 12:43
- EUFEPS workshop Helmut 2008-12-23 17:03