The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers

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...

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Veröffentlicht in:Biopharmaceutics & drug disposition 1999-10, Vol.20 (7), p.327-334
Hauptverfasser: Kanerva, Harri, Kilkku, Olavi, Heinonen, Esa, Helminen, Antti, Rouru, Juha, Tarpila, Simo, Scheinin, Mika, Huupponen, Risto, Klebovich, Imre, Drabant, Sandor, Urtti, Arto
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container_issue 7
container_start_page 327
container_title Biopharmaceutics & drug disposition
container_volume 20
creator Kanerva, Harri
Kilkku, Olavi
Heinonen, Esa
Helminen, Antti
Rouru, Juha
Tarpila, Simo
Scheinin, Mika
Huupponen, Risto
Klebovich, Imre
Drabant, Sandor
Urtti, Arto
description 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 Tmax was 2–4 h. The elimination half‐life increased from about 20 h to about 32 h with the increasing dose. Nevertheless, the AUC0–∞ 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. Cmax was reached at about 6 h. The AUC0–48 h for the N‐desmethyl metabolite was about one third of the AUC0–∞ of the parent compound and the ratio remained constant at each dose level. Deramciclane was safe, and was well tolerated at each dose level. Copyright © 1999 John Wiley & Sons, Ltd.
doi_str_mv 10.1002/(SICI)1099-081X(199910)20:7<327::AID-BDD192>3.0.CO;2-8
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Deramciclane was safe, and was well tolerated at each dose level. Copyright © 1999 John Wiley &amp; Sons, Ltd.</description><identifier>ISSN: 0142-2782</identifier><identifier>EISSN: 1099-081X</identifier><identifier>DOI: 10.1002/(SICI)1099-081X(199910)20:7&lt;327::AID-BDD192&gt;3.0.CO;2-8</identifier><identifier>PMID: 10760840</identifier><identifier>CODEN: BDDID8</identifier><language>eng</language><publisher>Chichester, UK: John Wiley &amp; Sons, Ltd</publisher><subject>Adult ; Area Under Curve ; Biological and medical sciences ; Biotransformation ; Blood Pressure - drug effects ; Bornanes - administration &amp; dosage ; Bornanes - adverse effects ; Bornanes - pharmacokinetics ; Chromatography, Liquid ; deramciclane ; deramciclane fumarate ; Double-Blind Method ; first administration ; Heart Rate - drug effects ; Humans ; Male ; Mass Spectrometry ; Medical sciences ; Neuropharmacology ; pharmacokinetics ; Pharmacology. 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Drug Dispos</addtitle><description>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 Tmax was 2–4 h. The elimination half‐life increased from about 20 h to about 32 h with the increasing dose. Nevertheless, the AUC0–∞ 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. 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Psychiatry</topic><topic>Psychopharmacology</topic><topic>Serotonin Antagonists - administration &amp; dosage</topic><topic>Serotonin Antagonists - adverse effects</topic><topic>Serotonin Antagonists - pharmacokinetics</topic><topic>tolerability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kanerva, Harri</creatorcontrib><creatorcontrib>Kilkku, Olavi</creatorcontrib><creatorcontrib>Heinonen, Esa</creatorcontrib><creatorcontrib>Helminen, Antti</creatorcontrib><creatorcontrib>Rouru, Juha</creatorcontrib><creatorcontrib>Tarpila, Simo</creatorcontrib><creatorcontrib>Scheinin, Mika</creatorcontrib><creatorcontrib>Huupponen, Risto</creatorcontrib><creatorcontrib>Klebovich, Imre</creatorcontrib><creatorcontrib>Drabant, Sandor</creatorcontrib><creatorcontrib>Urtti, Arto</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Biopharmaceutics &amp; drug disposition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kanerva, Harri</au><au>Kilkku, Olavi</au><au>Heinonen, Esa</au><au>Helminen, Antti</au><au>Rouru, Juha</au><au>Tarpila, Simo</au><au>Scheinin, Mika</au><au>Huupponen, Risto</au><au>Klebovich, Imre</au><au>Drabant, Sandor</au><au>Urtti, Arto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers</atitle><jtitle>Biopharmaceutics &amp; drug disposition</jtitle><addtitle>Biopharm. Drug Dispos</addtitle><date>1999-10</date><risdate>1999</risdate><volume>20</volume><issue>7</issue><spage>327</spage><epage>334</epage><pages>327-334</pages><issn>0142-2782</issn><eissn>1099-081X</eissn><coden>BDDID8</coden><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 Tmax was 2–4 h. The elimination half‐life increased from about 20 h to about 32 h with the increasing dose. Nevertheless, the AUC0–∞ 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. Cmax was reached at about 6 h. The AUC0–48 h for the N‐desmethyl metabolite was about one third of the AUC0–∞ of the parent compound and the ratio remained constant at each dose level. Deramciclane was safe, and was well tolerated at each dose level. Copyright © 1999 John Wiley &amp; Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley &amp; Sons, Ltd</pub><pmid>10760840</pmid><doi>10.1002/(SICI)1099-081X(199910)20:7&lt;327::AID-BDD192&gt;3.0.CO;2-8</doi><tpages>8</tpages></addata></record>
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subjects Adult
Area Under Curve
Biological and medical sciences
Biotransformation
Blood Pressure - drug effects
Bornanes - administration & dosage
Bornanes - adverse effects
Bornanes - pharmacokinetics
Chromatography, Liquid
deramciclane
deramciclane fumarate
Double-Blind Method
first administration
Heart Rate - drug effects
Humans
Male
Mass Spectrometry
Medical sciences
Neuropharmacology
pharmacokinetics
Pharmacology. Drug treatments
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Serotonin Antagonists - administration & dosage
Serotonin Antagonists - adverse effects
Serotonin Antagonists - pharmacokinetics
tolerability
title The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers
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