Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Methylphenidate in Healthy Adults

Clin Drug Investig. 2021 Feb;41(2):149-159. doi: 10.1007/s40261-020-00992-6. Epub 2020 Dec 23.

Abstract

Background and objectives: Viloxazine extended-release (viloxazine ER, SPN-812) is a novel non-stimulant with activity at serotonin receptors and the norepinephrine transporter, which is under investigation as a potential treatment for attention-deficit/hyperactivity disorder. Given the potential for viloxazine ER to be coadministered with other pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine ER + methylphenidate versus viloxazine ER or methylphenidate alone.

Methods: In this single-center, crossover, open-label trial, healthy adult participants received oral administration of 700 mg viloxazine ER alone, 36 mg methylphenidate alone, and combination viloxazine ER (700 mg) + methylphenidate (36 mg), with blood samples collected over 4 days post-administration. The active drug in viloxazine ER (viloxazine) and methylphenidate was measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events (AEs), vital signs, echocardiograms, and clinical laboratory evaluations.

Results: Of 36 healthy adults who were enrolled, 34 completed the trial. The geometric least squares mean ratios are reported as [combination/single drug (90% confidence intervals)]. For viloxazine ER, maximum measured plasma concentration (Cmax) = 100.98% (96.21-105.99), area under the concentration-time curve from time zero to the last measurable time (AUCt) = 98.62% (96.21-101.08), and area under the concentration-time curve from time zero to infinity (AUC) = 98.96% (96.55-101.44). For methylphenidate, Cmax = 103.55% (97.42-110.07), AUCt = 106.67% (101.01-112.64), and AUC = 106.61% (100.99-112.54). All reported AEs were mild in severity.

Conclusions: Coadministration of viloxazine ER and methylphenidate did not impact the pharmacokinetics of viloxazine or methylphenidate relative to administration of either drug alone. The combination appeared to be safe and well tolerated.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Central Nervous System Stimulants / administration & dosage*
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Female
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Methylphenidate / pharmacokinetics
  • Middle Aged
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Viloxazine / administration & dosage*
  • Viloxazine / pharmacokinetics
  • Young Adult

Substances

  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Norepinephrine Plasma Membrane Transport Proteins
  • SLC6A2 protein, human
  • Methylphenidate
  • Viloxazine