Bioequivalence and Bioavailability Forum

Dear Ahmed,

have a look at the European Guidance on BA/BE:
3.1 Design

[…] In such steady-state studies the administration scheme should follow the usual dosage recommendations.
[…] In steady-state studies wash out of the previous treatment last dose can overlap with the build-up of the second treatment, provided the build-up period is sufficiently long (at least three times the terminal half-life).
[…] In order to study bioavailability under steady-state conditions when differences between morning and evening or nightly dosing are known, (e.g. if it is known that the circadian rhythm is known to have an influence on bioavailability), sampling should be carried out over a full 24 hours cycle.

3.3 Characteristics to be investigated

[…] For studies in steady state AUC_τ, C_max, C_min and fluctuation should be provided.

APPENDIX I

AUC_τ: AUC during a dosage interval (τ) in steady state;
C_max: maximal plasma concentration;
C_min: minimal plasma concentration;
C_av: average plasma concentration;
Fluctuation: (C_max-C_min)/C_av.

C_av = AUC_τ/τ

Remarks:
For the design you should always apply a ‘worst-case-scenario’ for the half life, i.e., never use a mean value from the literature, but the longest reported half life (otherwise the superposition principle of pharmacokinetics [AUC_∞ from single dose = AUC_τ in steady state] is not valid).
Always take pre-dose samples during the saturation phase in order to check compliance.