Pharmacokinetic and statistical analyses.

Noncompartmental pharmacokinetic analysis (NCA) was performed using Phoenix WinNonLin, version 6.4 (Mountain View, CA), given the data-rich nature of the sampling schema. The following parameters were derived by NCA: maximum concentration (C_max), time to maximum concentration (T_max), last measurable concentration (C_last), time to last measurable concentration (T_last), area under the curve from time zero to the last measurable concentration (AUC_0–last), area under the curve from time zero to infinity (AUC_0–∞), volume of distribution during the terminal phase after intravenous administration (V_z), clearance (CL), and terminal half-life. Between-group comparisons of matched subjects were performed using the Wilcoxon matched-pair signed-rank test and Fisher's exact test for categorical variables. Visual inspection of the scatterplot matrix, Pearson's correlation (R), and ordinary least-square regression were used to assess the relationships between pharmacokinetic system parameters (CL and V_z) and body size. In addition, nonlinear regression (power function) was used to compare pharmacokinetic system parameters to weight^β and α(weight/median weight)^β, where β is an exponent and α is a constant function of weight. Discrimination between models was performed based on the coefficient of determination (R²) and the Akaike information criterion (AIC). All statistical analyses were implemented through STATA SE, version 13.1.