Multiple dose safety study, design

Accumulation ratio based on Cmax, Cmin, or AUC can be different. Accumulation estimated from Cmin comparison tends to overestimate, while AUC comparison gives the accumulation of overall exposure, and is not that sensitive to the variability of Cmin values [2], Estimating possible accumulation is also important for designing multiple dosing studies in drug safety studies. If a plasma concentration profile is available for a certain dose, superposition [3] should be used to estimate the plasma profile at steady state. RA can be estimated for the different exposure parameters. 

Open label study with three treatment groups, with multiple oral doses of 25 mg (Treatment Group I) and 50 mg (Treatment Group II) once daily, immediately after intake of a standard breakfast in a parallel-group design. Safety information and bioanalytical data were reviewed to determine the dose for Treatment Group III (multiple oral doses of 75 or 100 mg XYZ1234). 

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