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Pharmacokinetics of a Modified-Release Dexamphetamine Sulfate Formulation Following Single and Multiple Dosing in Healthy Adults: Comparative Bioavailability with Immediate-Release Dexamphetamine Sulfate, between Strengths, Assessment of Food and Meal Composition Effects

Henrik Uebel-von Sandersleben
Henrik Uebel-von Sandersleben
, 
Anke Mayer
Anke Mayer
, 
Michaela Ruhmann
Michaela Ruhmann
, 
Oliver Dangel
Oliver Dangel
 und 
Helmut Schütz
Helmut Schütz
   | 30. Nov. 2023
Scandinavian Journal of Child and Adolescent Psychiatry and Psychology's Cover Image
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Article Category: Research Article
Online veröffentlicht: 30. Nov. 2023
Seitenbereich: 132 - 142
DOI: https://doi.org/10.2478/sjcapp-2023-0014
Schlüsselwörter
© 2023 Henrik Uebel-von Sandersleben et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

FIGURE 1.

Geometric mean dexamphetamine plasma concentration-time profiles following single-dose administration of DEX-MR and DEX-IR in (a) fasted and (b) fed state.
Geometric mean dexamphetamine plasma concentration-time profiles following single-dose administration of DEX-MR and DEX-IR in (a) fasted and (b) fed state.

FIGURE 2

Geometric mean dexamphetamine plasma concentration-time profiles following administration of DEX-MR 20 mg and DEX-IR 10 mg b.i.d. after intake of a normocaloric (a) and a high-fat, high-calorie breakfast (b)
Geometric mean dexamphetamine plasma concentration-time profiles following administration of DEX-MR 20 mg and DEX-IR 10 mg b.i.d. after intake of a normocaloric (a) and a high-fat, high-calorie breakfast (b)

FIGURE 3.

Geometric mean dexamphetamine plasma concentration-time profiles at steady-state following administration of DEX-MR 20 mg and DEX-IR 10 mg b.i.d. after intake of (a) a normocaloric breakfast on day 6 and (b) a high-fat, high-calorie breakfast on day 7.
Geometric mean dexamphetamine plasma concentration-time profiles at steady-state following administration of DEX-MR 20 mg and DEX-IR 10 mg b.i.d. after intake of (a) a normocaloric breakfast on day 6 and (b) a high-fat, high-calorie breakfast on day 7.

PK metrics and food effect assessment – DEX-MR 10 mg (20 mg dose) and DEX-MR 20 mg (single-dose study), 28 subjects.

PK metric (unit) Geometric Least Squares Mean PE (%) 90% CI CVintra (%) CVinter (%)
DEX-MR 10 mg (1×2)
fasting fed
Cmax (ng/mL) 53.94 48.67 110.83 105.56 – 116.26 10.39 11.35
AUC0–t (h×ng/mL) 914.8 816.6 112.02 107.91 – 116.29 8.12 14.56
AUC0–∞ (h×ng/mL) 926.2 825.5 112.20 107.93 – 116.63 8.41 14.56
DEX-MR 20 mg (1×1)
fasting fed
Cmax (ng/mL) 53.98 47.53 113.58 107.45 – 120.05 12.06 10.23
AUC0–t (h×ng/mL) 871.8 817.8 106.61 102.43 – 110.96 8.68 11.59
AUC0–∞ (h×ng/mL) 882.0 828.7 106.44 102.16 – 110.89 8.91 11.78

Comparative bioavailabilities of DEX-MR (20 mg dose) and DEX-IR 10 mg b.i.d. under fasted and fed conditions (single-dose study), 28 subjects.

PK metric (unit) Geometric Least Squares Mean PE (%) 90% CI CVintra (%) CVinter (%)
Fasted conditions
DEX-MR 10 mg 1×2 DEX-IR 10 mg b.i.d.
Cmax (ng/mL) 53.94 57.82 93.29 91.26 – 95.36 4.78 12.40
AUC0–t (h×ng/mL) 914.8 884.4 103.43 99.81 – 107.18 7.75 15.11
AUC0–∞ (h×ng/mL) 926.2 895.6 103.41 99.66 – 107.30 8.03 15.39
DEX-MR 20 mg 1×1 DEX-IR 10 mg b.i.d.
Cmax (ng/mL) 53.98 57.82 93.35 90.71 – 96.08 6.24 10.25
AUC0–t (h×ng/mL) 871.8 884.4 98.57 95.91 – 101.31 5.94 16.16
AUC0–∞ (h×ng/mL) 882.0 895.6 98.48 95.77 – 101.27 6.06 16.66
DEX-MR 10 mg 1×2 DEX-MR 20 mg 1×1
Cmax (ng/mL) 53.94 53.97 99.95 97.15 – 102.82 6.18 11.26
AUC0–t (h×ng/mL) 914.3 872.2 104.82 101.94 – 107.79 6.09 15.22
AUC0–∞ (h×ng/mL) 925.7 882.5 104.90 101.91 – 107.98 6.31 15.51
Fed conditions
DEX-MR 10 mg 1×2 DEX-IR 10 mg b.i.d.
Cmax (ng/mL) 48.67 57.00 85.38 81.25 – 89.72 10.80 9.39
AUC0–t (h×ng/mL) 816.6 821.2 99.44 96.20 – 102.80 7.21 13.89
AUC0–∞ (h×ng/mL) 825.5 831.5 99.28 95.98 – 102.70 7.35 14.02
DEX-MR 20 mg 1×1 DEX-IR 10 mg b.i.d.
Cmax (ng/mL) 47.53 57.00 83.37 79.06 – 87.92 11.55 10.88
AUC0–t (h×ng/mL) 817.8 821.2 99.59 96.44 – 102.84 6.97 11.04
AUC0–∞ (h×ng/mL) 828.7 831.5 99.66 96.44 – 103.00 7.14 11.01
DEX-MR 10 mg 1×2 DEX-MR 20 mg 1×1
Cmax (ng/mL) 48.59 47.61 102.06 95.66 – 108.51 13.42 12.19
AUC0–t (h×ng/mL) 816.0 818.4 99.71 95.84 – 103.73 8.63 12.11
AUC0–∞ (h×ng/mL) 824.9 829.3 99.47 95.48 – 103.62 8.93 12.07

Comparative bioavailabilities of DEX-MR 20 mg and DEX-IR 10 mg b.i.d. after intake of a normocaloric breakfast and a high-fat, high-calorie breakfast (multiple-dose study), 46 subjects.

PK metric (unit) Geometric Least Squares Mean PE (%) 90% CI CVintra (%) CVinter (%)
Normocaloric breakfast (day 6)
DEX-MR 20 mg DEX-IR 10 mg b.i.d.
Cmax,ss (ng/mL) 64.08 67.31 95.20 93.18 – 97.26 6.13 14.16
Cτ,ss (h×ng/mL) 17.45 17.19 101.49 97.92 – 105.18 10.23 22.05
AUC0–τ,ss (h×ng/mL) 904.3 897.9 100.71 98.99 – 102.45 4.91 16.19
High-fat, high-calorie breakfast (day 7)
DEX-MR 20 mg DEX-IR 10 mg b.i.d.
Cmax,ss (ng/mL) 59.60 68.00 87.64 85.50 – 89.85 7.09 13.73
Cτ,ss (h×ng/mL) 19.58 18.38 106.51 102.63– 110.53 10.62 21.36
AUC0–τ,ss (h×ng/mL) 895.4 903.5 99.11 97.35 – 100.90 5.12 15.55

Comparative bioavailabilities of DEX-MR 20 mg and DEX-IR 10 mg b.i.d. after intake of a normocaloric vs. a high-fat, high-calorie breakfast (breakfast study), 20 subjects.

PK metric (unit) Geometric Least Squares Mean PE (%) 90% CI CVintra (%) CVinter (%)
Normocaloric breakfast
DEX-MR 20 mg DEX-IR 10 mg b.i.d.
Cmax (ng/mL) 48.16 55.48 86.79 83.89 – 89.79 6.16 13.42
AUC0–t (h×ng/mL) 955.8 989.5 96.60 92.98 – 100.36 6.93 18.12
AUC0–∞ (h×ng/mL) 982.5 1012.9 97.00 93.24 – 100.91 7.16 18.97
High-fat, high-calorie breakfast
DEX-MR 20 mg DEX-IR 10 mg b.i.d.
Cmax (ng/mL) 45.82 53.98 84.88 80.07 – 89.99 10.31 13.37
AUC0–t (h×ng/mL) 908.3 914.7 99.31 95.47 – 103.31 6.93 17.09
AUC0–∞ (h×ng/mL) 932.4 942.5 98.93 95.31 – 102.68 6.54 17.08
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