Bioequivalence and Bioavailability Forum • IR with t½ ≥ 24 h

IR with t½ ≥ 24 h [NCA / SHAM]

posted by Helmut – Vienna, Austria, 2025-10-14 12:30 (253 d 14:48 ago) – Posting: # 24451
Views: 2,671

Hi Darborn,

❝ When calculating AUC_0–∞, I know some regulatory agencies use extrapolation while others use the actual value. For a long half-life product truncated at 72 hours, should I use AUC_0–t or AUC_0–72 for bioequivalence assessment? :confused:

If it is an IR-product with a half life ≥ 24 h, AUC_0–72 (see this article about ICH M13A and the linked references).

If t_½ < 24 h, the primary metric is AUC_0–t. You have to estimate AUC_0–∞ as well but only to assess the extrapolated fraction (AUC_0–t should cover ≥ 80 % of AUC_0–∞ in ≥ 80 % of observations).

❝ I think these two value may differ when 72h has a LLOQ.

Of course. See this presentation (slides 19–24).

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Complete thread:

long half-life AUC0-t or AUC0-72 Darborn 2025-10-14 05:34 [NCA / SHAM]
- IR with t½ ≥ 24 hHelmut 2025-10-14 10:30
  - IR with t½ ≥ 24 h Darborn 2025-10-16 06:05
    - long half life product? Helmut 2025-10-16 08:13
      - long half life product? Darborn 2025-10-17 05:16
- long half-life AUC0-t or AUC0-72 ElMaestro 2025-10-15 17:41
  - long half-life AUC0-t or AUC0-72 Darborn 2025-10-16 06:00