Bioequivalence and Bioavailability Forum

Hi Brus,

❝ When you need to perform the study in patients due to tolerability/safety reasons, How do you perform the washout period in patients? (Between periods and before period 1 to avoid pre-dose concentrations in both periods).

A SD crossover is only possible for drugs in patients with a stable disease (e.g., theophylline in asthmatics). Otherwise, you have to opt for a parallel design.

• Get PK data from the literature. Don’t use the average half life, be conservative (example).
• Plan the study (first dose after the patients’ usual treatment, washout) with ≥ 5 × t_½. If that’s longer than the common dosing interval → SD not possible.
  
• Simulate concentrations (in Phoenix / Win­Non­lin’s ‘nonparametric superpostion’ module or even a spreadsheet) with your dose & regimen. If you would get pre-dose concentrations > 5% of C_max in a substantial number of subjects → SD not possible.
  
• If a SD study is not possible, you have to perform the study in steady state. Sorry.