English: Circulating mean dextroamphetamine concentrations (ng/mL) over 24 hours following oral administration of a single equimolar dose of dextroamphetamine sulfate immediate-release (IR) (40.3 mg; equivalent to 29.6 mg dextroamphetamine) (n=23) and lisdexamfetamine dimesylate (100 mg) (n=24) in healthy non-stimulant-using young adults.

Sources of the data (Figure 1 and Figure 2A, respectively):

• (2017). "Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects". Front Pharmacol 8: 617. DOI:10.3389/fphar.2017.00617. PMID 28936175. PMC: 5594082.
• (February 2019). "Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study". J Steroid Biochem Mol Biol 186: 212–225. DOI:10.1016/j.jsbmb.2018.10.016. PMID 30381248.

Figure caption from original source:

FIGURE 1. Amphetamine concentration-time curves (mean ± SEM) in 24 and 23 subjects after administration of lisdexamfetamine and D-amphetamine, respectively. The onset and peak times of the amphetamine concentration-time curve were longer after lisdexamfetamine administration compared with D-amphetamine administration, but no differences were found in the maximal concentrations, areas under the concentration-time curves, or absorption or elimination constants between the two treatments. The inset shows the semilogarithmic plot. The amphetamine concentration-time curves were shifted to the right after lisdexamfetamine administration compared with D-amphetamine administration but were otherwise almost identical. The drugs were administered at t = 0. The corresponding pharmacokinetic parameters were derived from compartmental and non-compartmental analyses and are shown in Table 1 and Supplementary Table S1, respectively.

Error bars are provided in the original graphs and points are mean ± SEM.

Pharmacokinetics described as follows in the results section from original source:

The plasma amphetamine concentration-time curves after D-amphetamine and lisdexamfetamine administration are shown in Figure 1. Individual plots are shown in Supplementary Figure S1. The intravenous catheter could not be placed and plasma was not collected in one subject after D-amphetamine administration. The corresponding pharmacokinetic parameters that were derived from the compartmental and non-compartmental analyses are shown in Table 1 and Supplementary Table S1, respectively. As planned, the administration of equimolar doses of D-amphetamine and lisdexamfetamine resulted in similar AUC values. The increase in plasma amphetamine concentrations had a 0.6 ± 0.6 h (mean ± SD) longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared with D-amphetamine administration (Figure 1, Table 1, and Supplementary Table S1). Both Tlag and Tmax values were significantly different (t = 2.87, p < 0.001, and t = 3.54, p < 0.001, respectively; Table 1) between the two active drug conditions. However, the absorption constant, K01, was only non-significantly greater after D-amphetamine administration compared with lisdexamfetamine administration (t = 1.86, p = 0.07). Cmax values were similar (Table 1 and Supplementary Table S1) after the administration of both drugs. Thus, in contrast to our hypothesis, a curve shift was observed, but no relevant difference in the shape or peak size of the two amphetamine concentration-time curves was found (Figure 1). There were no differences in the pharmacokinetics of lisdexamfetamine or D-amphetamine between men and women.

In Table 1, the following values were reported (geometric mean (range)):

• C_max: 120 (77–181) ng/mL for dextroamphetamine and 118 (83–174) ng/mL for lisdexamfetamine
• t_lag: 0.8 (0.3–2.0) hours for dextroamphetamine and 1.5 (0.8–2.4) hours for lisdexamfetamine
• t_max: 3.3 (0.9–5.9) hours for dextroamphetamine and 4.6 (2.5–8.4) hours for lisdexamfetamine
• t_1/2: 7.9 (4.3–15) hours for dextroamphetamine and 7.9 (4.7–13) hours for lisdexamfetamine
• AUC_∞: 1727 (1116–3463) ng/mL·h for dextroamphetamine and 1817 (1087–3031) ng/mL·h for lisdexamfetamine