PMC

PopPK model structure of modafinil acid, combined with the model of modafinil, comprises of four compartments: gastrointestinal tract (GI), central and peripheral compartment for modafinil, and central compartment for modafinil acid. X1, V1, X2, and V2 are amount (X) and volume of distribution (V) of modafinil in central (systemic circulation and liver) and peripheral (tissues) compartments, respectively. And X3 and V3 are amount and volume of distribution of modafinil acid in its central compartment. Rate constants for the compartments are Ka (absorption), K12, K21, K1m (modafinil is metabolized into modafinil acid) and Km (elimination from central compartment for modafinil acid). F₁ is the bioavailability of modafinil, while F₂ is the conversion fraction of modafinil to modafinil acid.

Effects of modafinil at acquisition (A; trials to criterion) and retention (B; TRAINING bars represent the first training latency, and TEST bars represent the test latency) on the inhibitory avoidance response in non-sleep–deprived animals (Experiment 1). V refers to the group of rats that received vehicle; MODA 100, rats that received 100 mg/kg of modafinil; MODA 200 rats that received 200 mg/kg of modafinil (*P < 0.05 compared with V). Effects of modafinil on the inhibitory-avoidance acquisition (C; trials to criterion) and retention (D TRAINING BARS represent the first training latency, and TEST bars represent the test latency) after sleep deprivation (Experiment 2). CC-V refers to cage control animals that received vehicle; CC-MODA 100, cage control animals that received 100 mg/kg of modafinil; CC-MODA 200, that received 200 mg/kg of modafinil; SD-V, sleep-deprived animals that received vehicle; SD-MODA 100, sleep-deprived animals that received 100 mg/kg of modafinil; SD-MODA 200, sleep-deprived animals that received 200 mg/kg of modafinil. The number of animals is shown in parentheses; ^#P < 0.05 comparing control animals and SD-MODA 100 groups during the same test session.

Individual plot of individual predictions and observations versus time. The square is observed concentration of modafinil. The dashed line is individual prediction of modafinil. The solid circle is observed concentration of modafinil acid. The solid line is individual prediction of modafinil acid.

Effect of modafinil treatment on the Y-maze learning task. (A) Effect of modafinil at concentrations of 100, 200, and 300 mg/kg on the accuracy rates for the Y-maze learning task (n=8). (B) Effects of modafinil at concentrations of 100, 200, and 300 mg/kg on the number of trials required to achieve the learning criterion in the Y-maze task (n=8). ^*P<0.05 and ^**P<0.01 compared with the control group. M100, modafinil 100 mg/kg; M200, modafinil 200 mg/kg; M300, modafinil 300 mg/kg.