Where AUC could be extrapolated to infinity, the extrapolated area generally represented less than 10% of the total AUC.
AUC extrapolated percent of the AUC extrapolated, AUC INF area under the curve extrapolated to infinity, CMAX maximum plasma concentration, T ½ λz terminal half-life, λz terminal rate constant, MRT mean residence time extrapolated to infinity, TMAX time to CMAX, F fraction of the dose absorbed.
The total AUC extrapolated to infinity (AUC0 inf) was computed by combining AUC0 last time point with an extrapolated value.
Mean areas under the plasma concentration versus time curves extrapolated to infinity were 2100 ng h/mL and 5160 ng h/mL for the topical and intravenous doses, respectively.
Estimates were determined for the pharmacokinetic parameters: alpha half-life (t 1/2α), beta half-life (t 1/2β), area under the curve extrapolated to infinity (AUC0-∞) and mean residence time (MRT).
The geometric mean ratios (MPH-MLR/IR methylphenidate [90 % CI]) of log-transformed area under the plasma drug concentration-time curve to the last measurable observation (day 1: 0.88 [84.75-91.80]; day 4: 0.84 [81.16-86.94]), and area under the plasma drug concentration extrapolated to infinity (day 1: 0.93 [88.57-97.28]; day 4: 0.88 [84.48-91.17]) were within the 80-125 % bioequivalence range.
Both models used in this study can predict the EUR; for the logistic growth model the carrying capacity is a parameter in the fitting, and for the parallel flow model the function converges to a finite value when extrapolated to infinity.
AUC extrapolated to infinity (AUCinf) was calculated as AUClast + Clast/ λz (where Clast is the last quantifiable concentration).
The area under the concentration versus time curve (AUC) was calculated using the trapezoidal rule and extrapolated to infinity.
When possible, the total AUC (AUCtot) was extrapolated to infinity by dividing λz into the predicted plasma concentration at the end of the sampling interval.
The primary end point was metformin absorption, estimated by the area under the curve (AUC) of the plasma drug concentration from time 0 extrapolated to infinity (AUC0 ∞).
