The absolute bioavailability of racemic ketamine from a novel sublingual formulation

AIM: The principal study objective was to investigate the pharmacokinetic characteristics of a new sublingual ketamine wafer and to establish its absolute bioavailability and local tolerability. METHODS: The study was of open label, two way randomized crossover design in eight healthy male volunteer...

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Main Authors: Rolan, P., Lim, Stephen, Sunderland, Bruce, Liu, Yandi, Molnar, V.
Format: Journal Article
Published: Blackwell Publishing 2014
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/25299
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author Rolan, P.
Lim, Stephen
Sunderland, Bruce
Liu, Yandi
Molnar, V.
author_facet Rolan, P.
Lim, Stephen
Sunderland, Bruce
Liu, Yandi
Molnar, V.
author_sort Rolan, P.
building Curtin Institutional Repository
collection Online Access
description AIM: The principal study objective was to investigate the pharmacokinetic characteristics of a new sublingual ketamine wafer and to establish its absolute bioavailability and local tolerability. METHODS: The study was of open label, two way randomized crossover design in eight healthy male volunteers. Each participant received either a single 10 mg intravenous dose as a constant rate 30 min infusion or a 25 mg sublingual dose of ketamine wafer in two treatment periods with a 7 day wash out. Pharmacokinetic blood sampling and local tolerability and safety assessments were carried out during 24 h following both dosing occasions. Plasma concentrations were analyzed by non-compartmental methods and local tolerability was assessed using modified Likert scales. RESULTS: The median (90% CI lower, upper limit) absolute bioavailability of sublingual ketamine was 29% (27, 31%). The first quantifiable plasma ketamine concentration was observed within 5 min for all eight participants for both routes of administration and the median (min–max) time of the peak plasma concentration was 0.75 h (0.25–1.0 h) after sublingual administration. The ketamine wafer had very good local tolerability. CONCLUSION: Sublingual administration of the ketamine wafer resulted in rapid absorption. The ketamine wafer has comparable bioavailability with other oral transmucosal formulations of ketamine but with markedly reduced inter-subject variability, warranting further evaluation as analgesic adjunct.
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spelling curtin-20.500.11937-252992017-09-13T15:19:09Z The absolute bioavailability of racemic ketamine from a novel sublingual formulation Rolan, P. Lim, Stephen Sunderland, Bruce Liu, Yandi Molnar, V. ketamine sublingual bioavailability pharmacokinetics AIM: The principal study objective was to investigate the pharmacokinetic characteristics of a new sublingual ketamine wafer and to establish its absolute bioavailability and local tolerability. METHODS: The study was of open label, two way randomized crossover design in eight healthy male volunteers. Each participant received either a single 10 mg intravenous dose as a constant rate 30 min infusion or a 25 mg sublingual dose of ketamine wafer in two treatment periods with a 7 day wash out. Pharmacokinetic blood sampling and local tolerability and safety assessments were carried out during 24 h following both dosing occasions. Plasma concentrations were analyzed by non-compartmental methods and local tolerability was assessed using modified Likert scales. RESULTS: The median (90% CI lower, upper limit) absolute bioavailability of sublingual ketamine was 29% (27, 31%). The first quantifiable plasma ketamine concentration was observed within 5 min for all eight participants for both routes of administration and the median (min–max) time of the peak plasma concentration was 0.75 h (0.25–1.0 h) after sublingual administration. The ketamine wafer had very good local tolerability. CONCLUSION: Sublingual administration of the ketamine wafer resulted in rapid absorption. The ketamine wafer has comparable bioavailability with other oral transmucosal formulations of ketamine but with markedly reduced inter-subject variability, warranting further evaluation as analgesic adjunct. 2014 Journal Article http://hdl.handle.net/20.500.11937/25299 10.1111/bcp.12264 Blackwell Publishing unknown
spellingShingle ketamine
sublingual
bioavailability
pharmacokinetics
Rolan, P.
Lim, Stephen
Sunderland, Bruce
Liu, Yandi
Molnar, V.
The absolute bioavailability of racemic ketamine from a novel sublingual formulation
title The absolute bioavailability of racemic ketamine from a novel sublingual formulation
title_full The absolute bioavailability of racemic ketamine from a novel sublingual formulation
title_fullStr The absolute bioavailability of racemic ketamine from a novel sublingual formulation
title_full_unstemmed The absolute bioavailability of racemic ketamine from a novel sublingual formulation
title_short The absolute bioavailability of racemic ketamine from a novel sublingual formulation
title_sort absolute bioavailability of racemic ketamine from a novel sublingual formulation
topic ketamine
sublingual
bioavailability
pharmacokinetics
url http://hdl.handle.net/20.500.11937/25299