Figure 2.

Intrasubject variability in the total amount of unchanged active substance excreted in the urine (T_Ae) and the maximum rate of drug excretion (R_max) seen with brand‐name and generic formulations of alendronate (10 mg) in a replicate design bioequivalence study (n = 26). (A) Distribution of T_Ae in the trial population after administration of the brand‐name or generic formulation of alendronate (R1, R2, T1 or T2); lines indicate the T_Ae levels per subject. (B) Difference plots for the ln‐transformed treatment ratios for T_Ae (T1 : R1, T2 : R2 and T1 : T2), corrected by the brand‐name drug ratios (R1 : R2) in individuals. (C) Difference plots for the ratios corrected by the generic drug ratios (T1 : T2). (G) Correlation of the generic ratios (y‐axis) and the brand‐name ratios (x‐axis) for T_Ae on a logarithmic scale. (H) Correlation of generic : brand‐name ratios (T1 : R1 and T2 : R2) after the first and second drug administration. (D, E, F, I and J) Graphs of R_max in the same sequence for T_Ae. Intrasubject variability based on the other eight bioequivalence studies is shown in Supplementary Figures S1–3