Bioequivalence and Bioavailability Forum

Calculation of AUC0-72 [NCA / SHAM]

posted by Helmut  – Vienna, Austria, 2009-01-26 17:24 (5562 d 07:43 ago) – Posting: # 3123
Views: 26,174

Dear D. Labes,

sorry for the late response – I was driven by discussions about the drafted European BE-Guideline.

❝ I would like to discuss this a bit further.

❝ How do you act in a truncated setting if the last sample is missing? Or if some subject has conc. <LOQ due to faster kinetics?

❝

❝ Omit this subject from the analysis?

I have heard of CROs omitting subjects if AUC₇₂ was stated as the primary parameter and the sample at 72 h (or earlier) was ≤LOQ. In the strict sense I would consider this correct.
But: with the current trend of moving from seening BE as a surrogate of clinical safety/efficacy to a measure of pharmaceutical performance in vivo I would go with Kamal Midha’s Mantra and accept AUCs where the absorption is completed (C_last ≥2–4 times t_max). See Example 2 in this thread. If we truncate AUCs of subjects with C_last<72 (for any treatment) at the last time point where C>LOQ (for all treatments), it should be possible to get an unbiased estimate of the T/R-ratio.* Unfortunately this method is not available in commercial software (at least not in the current versions of WinNonlin, Kinetica, EquivTest/PK).

I wouldn’t start trying to get an estimate of C₇₂.

---

Edit (years later)

• Fisher D, Kramer W, Burmeister Getz E. Evaluation of a Scenario in Which Estimates of Bioequivalence Are Biased and a Proposed Solution: t_last (Common). J Clin Pharm. 2016;56(7):794–800. doi:10.1002/jcph.663. free resource.

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


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Science Quotes

Complete thread:

• Calculation of AUC0-72 Sasi 2008-06-10 10:44 
  • Calculation of AUC0-72 Jaime_R 2008-06-10 12:18
    • Calculation of AUC0-72 Ohlbe 2008-06-10 17:28
      • Calculation of AUC0-72 Jaime_R 2008-06-10 18:45
        • Regulators truncated d_labes 2009-06-18 09:26
          • Regulators truncated Ohlbe 2009-06-18 10:37
          • Regulators truncated Helmut 2009-06-18 14:49
            • Regulators truncated d_labes 2009-06-18 15:26
              • Regulators truncated Helmut 2009-06-18 15:44
                • Regulators truncated ElMaestro 2009-06-19 22:16
                  • Regulators truncated Helmut 2009-06-19 22:35
          • Luke 23:34 ElMaestro 2009-06-18 14:50
      • Calculation of AUC0-72 d_labes 2008-09-05 15:00
        • Calculation of AUC0-72Helmut 2009-01-26 16:24
          • Calculation of AUC0-72 d_labes 2009-01-26 16:57
            • Calculation of AUC0-72 Helmut 2009-01-26 17:20
              • The missing 72h d_labes 2009-01-27 11:48
                • The missing 72h Ohlbe 2009-01-28 00:00
                  • sensitivity analyses ? martin 2009-01-28 08:26
                  • Regulators ways are inscrutable d_labes 2009-01-28 09:54
                    • Regulators ways are inscrutable (at least the French) Ohlbe 2009-01-28 10:16
                • The missing 72h ElMaestro 2009-01-28 14:32
                  • Page 3848 of 221 d_labes 2009-01-28 14:51
                • Partial AUC calculation Astea 2017-03-11 20:14
                  • Partial AUC calculation mittyri 2017-03-16 19:46
  • Calculation of AUC0-72 PharmCat 2022-12-21 20:49