Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults.
Administration, Oral
Adrenergic Uptake Inhibitors
/ administration & dosage
Adult
Area Under Curve
Central Nervous System Stimulants
/ administration & dosage
Cross-Over Studies
Delayed-Action Preparations
Drug Interactions
Female
Humans
Lisdexamfetamine Dimesylate
/ administration & dosage
Male
Middle Aged
Viloxazine
/ administration & dosage
Young Adult
Journal
Journal of clinical psychopharmacology
ISSN: 1533-712X
Titre abrégé: J Clin Psychopharmacol
Pays: United States
ID NLM: 8109496
Informations de publication
Date de publication:
Historique:
pubmed:
16
2
2021
medline:
27
10
2021
entrez:
15
2
2021
Statut:
ppublish
Résumé
Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone. In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (d-amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations. Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33-100.82), area under the concentration-time curve from 0 to the last measurable time (AUC0-t) = 99.19% (96.53-101.91), and area under the concentration-time curve from 0 to infinity (AUCinf) = 99.23% (96.61-101.93). Lisdexamfetamine: Cmax = 112.78% (109.93-115.71), AUC0-t = 109.64% (105.25-114.22), and AUCinf = 109.52% (105.19-114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity. Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or d-amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated.
Sections du résumé
BACKGROUND
BACKGROUND
Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone.
METHODS
METHODS
In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (d-amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations.
RESULTS
RESULTS
Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33-100.82), area under the concentration-time curve from 0 to the last measurable time (AUC0-t) = 99.19% (96.53-101.91), and area under the concentration-time curve from 0 to infinity (AUCinf) = 99.23% (96.61-101.93). Lisdexamfetamine: Cmax = 112.78% (109.93-115.71), AUC0-t = 109.64% (105.25-114.22), and AUCinf = 109.52% (105.19-114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity.
CONCLUSIONS
CONCLUSIONS
Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or d-amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated.
Identifiants
pubmed: 33587403
doi: 10.1097/JCP.0000000000001361
pii: 00004714-202103000-00012
pmc: PMC7919699
doi:
Substances chimiques
Adrenergic Uptake Inhibitors
0
Central Nervous System Stimulants
0
Delayed-Action Preparations
0
Viloxazine
5I5Y2789ZF
Lisdexamfetamine Dimesylate
SJT761GEGS
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
155-162Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
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