Premium
Pharmacokinetics and central nervous system effects of the novel dual NK 1 /NK 3 receptor antagonist GSK 1144814 in alcohol‐intoxicated volunteers
Author(s) -
te Beek Erik T.,
Hay Justin L.,
Bullman Jonathan N.,
Burgess Clare,
Nahon Kimberly J.,
Klaassen Erica S.,
Gray Frank A.,
Gerven Joop M. A.
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12004
Subject(s) - crossover study , pharmacokinetics , pharmacology , placebo , epworth sleepiness scale , medicine , anesthesia , psychology , polysomnography , apnea , alternative medicine , pathology
Aims Antagonism of both NK 1 and NK 3 receptors may be an effective strategy in the pharmacotherapy of schizophrenia, drug addiction or depression. GSK 1144814 is a novel selective dual NK 1 /NK 3 receptor antagonist. The potential influence of GSK1144814 on the effects of alcohol was investigated. Methods In a blinded, randomized, placebo‐controlled, two period crossover study, the pharmacokinetics and central nervous system ( CNS ) effects of single oral doses of 200 mg GSK 1144814 were evaluated in 20 healthy volunteers, using a controlled alcohol infusion paradigm to maintain stable alcohol concentrations with subsequent analysis of eye movements, adaptive tracking, body sway, visual analogue scales, Epworth sleepiness scale and the verbal visual learning test. Results Frequent adverse effects were mild somnolence, fatigue and headache. Plasma concentration of GSK 1144814 in the presence of alcohol was maximal 1.5 h after dose administration. GSK 1144814 did not affect alcohol pharmacokinetics. Co‐administration of GSK 1144814 and alcohol impaired saccadic reaction time and peak velocity, adaptive tracking, alertness, sleepiness, word recognition and recognition reaction time compared with administration of alcohol alone, but the size of the interaction was small. Conclusions Administration of GSK 1144814 in the presence of alcohol was generally well tolerated and not likely to produce clinically relevant additional impairments after alcohol consumption.