AIMThe pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg -1 alcohol using 40% vodka).
METHODSIn a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration.
RESULTSAlcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated.
CONCLUSIONSMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Sodium oxybate (SO) has been approved for the treatment of alcohol dependence in Europe. Post-market surveillance has found no significant safety issues in alcohol relapsing patients taking SO, even though SO and alcohol share several pharmacological targets and effects.• Illicit SO (also called 'street GHB' or 'liquid ecstasy') can lead to abuse, misuse, addiction, criminal use and/or overdosing, and may have long term neurotoxic effects.• SMO.IR, a solid immediate-release formulation of sodium oxybate, is being developed to reduce the risk of criminal or accidental misuse of the drug and to obtain worldwide approval for the treatment of alcohol dependence.
WHAT THIS STUDY ADDS• SMO.IR and alcohol have distinct adverse effect profiles. The objective sedative effects of SMO.IR are much less marked than those of alcohol and no interaction was observed.• The dose of SMO.IR used in this study (2.25 g) is in the upper range of the therapeutic interval for alcohol dependence and is 30%-80% higher than commonly prescribed doses.• The low level of interaction between alcohol and SMO.IR may account for the good safety profile of the drug even in the context of alcohol relapses.
IntroductionSodium oxybate (SO) is the name of the sodium salt of gamma-hydroxybutyric acid when used as a therapeutic agent. Gamm...