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The first-order conditional estimation method with interaction was used throughout the model-building process. Tools used to evaluate and visualize the model were RStudio version 0.

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First-order, zero-order and Michaelis—Menten absorption models with and without lag time were evaluated in combination with one- and two-compartment distribution models.

Between-subject variability BSV; variability between individual subjects and between-occasion variability BOV; variability between the doses in an individual subject were tested using an exponential variance model. Residual unexplained variability RUV was evaluated with a combined additive and proportional error model.

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