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Asenapine Safety, Tolerability, and Pharmacokinetics After Single and Multiple Doses in Healthy Volunteers
Author(s) -
Dogterom Peter,
Timmer Cees,
Greef Rik,
Spaans Edwin,
Vries Dick,
Vliet Andre,
Peeters Pierre
Publication year - 2012
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1177/2160763x12455328
Subject(s) - tolerability , medicine , pharmacokinetics , asenapine , placebo , adverse effect , dosing , somnolence , dose , pharmacology , anesthesia , lithium (medication) , pathology , alternative medicine , bipolar disorder
This double‐blind, placebo‐controlled, randomized study is the first in healthy volunteers to describe the safety, tolerability, and pharmacokinetics of sublingual asenapine at therapeutic dosages. After a 2‐day placebo run‐in phase, healthy male volunteers received placebo or asenapine escalated to dosages of 3, 5, 10, or 15 mg bid. Another group received single doses (2 and 5 mg) 1 week apart. Serial blood samples were obtained for pharmacokinetic analysis. The single asenapine doses and multiple bid doses up to 10 mg were well tolerated. The most frequent treatment‐emergent adverse events were somnolence, oral paresthesia, fatigue, headache, dizziness, and dyspnea. Clinically relevant abnormalities or trends in laboratory and vital signs measures, physical examinations, or electrocardiograms were not observed. Asenapine was rapidly absorbed, with a t max of ∼1 hour, and was biphasically eliminated with a terminal elimination half‐life of 20 to 30 hours. In the range of 3 to 10 mg bid, increases in plasma concentrations were less than dose proportional. Asenapine appears to be well tolerated at single doses up to 5 mg and multiple doses up to 10 mg bid and can be administered to healthy volunteers in clinical pharmacology studies using the dosing regimens described.