Bioequivalence and Bioavailability Forum

Hi Biostats,

❝ Is there any scientific method or formula to calculate the time point for truncating the partial AUC (cutoff time point)?

Scientific? Yes. That would be based on PD – not PK as the GL recommends (regulations ≠ science). Examples of biphasic MR products:

• Methylphendiate (3 hours fasting and 4 hours fed).
  
• Zolipidem (1.5 hours fasting and fed).

The first part is for rapid onset of effect and the second for its maintenance. In both cases the cut-off points are based on clinical studies and the justification as given by the FDA.

If have seen studies trying to show BE to Concerta with a cut-off of 2 hours. That’s ridiculous. In many subjects we don’t see a trough between the IR and MR parts in the profiles (only a “shoulder”). Expect large intra-subject variability and opt for reference-scaling (requires a replicate design).