DOV 216,303, a "triple" reuptake inhibitor: Safety, tolerability, and pharmacokinetic profile

Bernard Beer, Jill Stark, Philip Krieter, P. Czobor, Gary Beer, Arnold Lippa, Phil Skolnick

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

This report describes the first evaluation in humans of DOV 216,303, a putative antidepressive that inhibits the reuptake of norepinephrine, serotonin, and dopamine. Subjects received single oral doses of 5 to 150 mg of DOV 216,303 or placebo. At 150 mg, 4 of 7 subjects reported gastrointestinal disturbances. In the multiple-dose phase of the evaluation, subjects received total daily doses of 50, 75, or 100 mg of DOV 216,303 or placebo for 10 days. At a total daily dose of 100 mg, gastrointestinal disturbances were reported in 4 of 6 volunteers. In both the single- and multiple-dose evaluations, no significant changes were noted in vital signs, electrocardiogram, hematology, or clinical chemistry. DOV 216,303 was rapidly absorbed (plasma tmax of 0.7-1.2 hours and t1/2 of 3.3-4.4 hours), with dose-proportional C max and AUC values. Furthermore, no remarkable difference was apparent in either the Cmax or AUCτ of DOV 216,303 following 1 and 10 days of dosing. The present results demonstrate that DOV 216,303 is safe and well tolerated both at single doses of up to 100 mg and multiple doses of up to 100 mg/day for 10 days. Plasma concentrations of DOV 216,303 after doses >10 mg exceed its reported IC50 values for inhibition of biogenic amine reuptake.

Original languageEnglish
Pages (from-to)1360-1367
Number of pages8
JournalJournal of Clinical Pharmacology
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 2004

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Pharmacokinetics
Safety
Area Under Curve
Placebos
Clinical Chemistry
Biogenic Amines
Vital Signs
Hematology
1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride
Inhibitory Concentration 50
Volunteers
Dopamine
Serotonin
Norepinephrine
Electrocardiography

Keywords

  • Antidepressives
  • DOV 216,303
  • Drug safety
  • Pharmacokinetics
  • Triple reuptake inhibitors

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

DOV 216,303, a "triple" reuptake inhibitor : Safety, tolerability, and pharmacokinetic profile. / Beer, Bernard; Stark, Jill; Krieter, Philip; Czobor, P.; Beer, Gary; Lippa, Arnold; Skolnick, Phil.

In: Journal of Clinical Pharmacology, Vol. 44, No. 12, 12.2004, p. 1360-1367.

Research output: Contribution to journalArticle

Beer, Bernard ; Stark, Jill ; Krieter, Philip ; Czobor, P. ; Beer, Gary ; Lippa, Arnold ; Skolnick, Phil. / DOV 216,303, a "triple" reuptake inhibitor : Safety, tolerability, and pharmacokinetic profile. In: Journal of Clinical Pharmacology. 2004 ; Vol. 44, No. 12. pp. 1360-1367.
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