title: The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers.
abstract: The pharmacokinetics and tolerability of a new putative non-benzodiazepine type anxiolytic compound deramciclane was studied in two consecutive studies. An open dose-escalation design was used to study doses from 0.2 to 50 mg in 18 healthy male volunteers. In the second study doses from 50 to 150 mg were investigated in 14 healthy males in a double-blind, placebo-controlled, dose escalation study. Deramciclane was rapidly absorbed from the GI-tract and T(max) was 2-4 h. The elimination half-life increased from about 20 h to about 32 h with the increasing dose. Nevertheless, the AUC(0-infinity) values increased linearly within the studies over the dose ranges of 3-50 and 50-150 mg. However, the increase was more than the ratio of the dose over the total dose range of 3-150 mg. Therefore, non-linear pharmacokinetics of deramciclane at high doses cannot be excluded. N-desmethyl deramciclane, which is the active metabolite of deramciclane, was determined in plasma. C(max) was reached at about 6 h. The AUC(0-48 h) for the N-desmethyl metabolite was about one third of the AUC(0-infinity) of the parent compound and the ratio remained constant at each dose level. Deramciclane was safe, and was well tolerated at each dose level.
authors.affiliation: Orion Corporation, Orion Pharma, Product Development, Espoo, Finland. harri.kanerva@orion.mailnet.fi
authors.forename: H
authors.initials: H
authors.lastname: Kanerva
authors.forename: O
authors.initials: O
authors.lastname: Kilkku
authors.forename: E
authors.initials: E
authors.lastname: Heinonen
authors.forename: A
authors.initials: A
authors.lastname: Helminen
authors.forename: J
authors.initials: J
authors.lastname: Rouru
authors.forename: S
authors.initials: S
authors.lastname: Tarpila
authors.forename: M
authors.initials: M
authors.lastname: Scheinin
authors.forename: R
authors.initials: R
authors.lastname: Huupponen
authors.forename: I
authors.initials: I
authors.lastname: Klebovich
authors.forename: S
authors.initials: S
authors.lastname: Drabant
authors.forename: A
authors.initials: A
authors.lastname: Urtti
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D001892:Camphanes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
chemical_list: D001892:Camphanes; D012702:Serotonin Antagonists; C060555:deramciclane