Bioequivalence and Bioavailability Forum

Dear Nirali!

❝ 2) if AUC %extrapolation is <20%, it assures that absorbtion process is

❝ complete. Thus, we can consider that subject for PK and statistical

❝ analysis and compare profile of test and referece product.

See the first plot in this post. The absorption phase (red line) is almost complete after 2 hours. Imagine a situation where both formulations give identical profiles (F_T=F_R; blue line) and one sample of T is missing at 6 hours. Both AUC_t will be >80% of AUC_inf (T: AUC₅ 41.5, 83.1% of AUC_inf; R: AUC₆ 44.3, 88.7%). Following your suggestion (absorption complete, comparing AUC_t) would lead to a biased result of F=93.7% (see also this post).

• Comparison of AUC_inf is unbiased - if a reliable estimate of t_½ for both formulations is possible (n>3, first time point in estimation >2-4times t_max).
  
• Comparison of AUC_ts, where t_last of formulations is different is biased.
  
• Truncation of both AUCs at the smaller t_last is unbiased.
  
• Imputation of an estimated C_last is unbiased (see also this post).

The regulatory acceptance of the last two options is unclear. IMHO if stated in the protocol or SAP no big deal (at least I am using the last method for many years without any problems).