Favorite Datasets from Early Phases of Drug Research

Relative Bioavailability Study

Part 6 - Table 1

Fourteen healthy male subjects (Sub) were allocated randomly to one of two treatment sequences (Seq) in a two period crossover design. The two treatment sequences were either one 40mg tablet, 1x40mg, given in the first treatment period followed by four 10mg tablets, 4x10mg, given simultaneously in the second treatment period (sequence 1/4), or the reverse ordering was administered (4/1). A washout period separated the treatment periods.

Two pharmacokinetic variables, area-under-the-plasma-concentration-vs.-time curve from zero to 72 hours, AUC (ng·hr/mL), and maximum plasma concentration, Cmax (ng/mL), were estimated for each subject in each treatment period from plasma levels of the parent compound (P), and its active metabolite (M), based upon plasma samples taken at pre dose and at various times up to 72 hours post dose.

• Are the average bioavailabilities of the two formulations, 1x40mg tablet and 4x10mg tablets, within 30% when considering both the parent compound (P) and the active metabolite (M)?
• Are there any notable carryover (confounded with both sequence and treatment-by-period interaction), period, or treatment effects? If so, can these be explained?
• Are there individual subjects whose paired results could be labeled as either concordant or discordant bivariate outliers?
• How well does a normal theory model fit?