Sodium acetate 3mmol/50ml / Sodium oxybate 2mmol/50ml / Sodium propionate 1.5mmol/50ml enema

Abstract Sodium oxybate (SMO) has shown efficacy in the treatment of alcohol withdrawal syndrome (AWS) and in the maintenance of abstinence in alcohol dependent (AD) patients in a series of pilot randomized controlled trials. SMO is marketed in these indications in Italy and Austria since 1991 and 1999, respectively. To expand access to SMO for the treatment of AD in other EU countries and since regulatory standards have evolved, a clinical development and research project in accordance with regulatory guidelines has been initiated in the maintenance of abstinence to further support the already available data. Phase 2 and 3 studies in AD patients were conducted. Results of this development program showed efficacy of SMO in the maintenance of abstinence in AD patients. Since heterogeneity of SMO treatment effect between studies was identified, various analyses explored the potential moderators of SMO efficacy. SMO efficacy was larger in high-severity AD population and with longer treatment duration. SMO was well tolerated both in regular clinical use and in clinical trials.Disclosure of InterestJ. Guiraud Shareolder of: Vergio, Employee of: Vergio

Abstract licence: CC BY 4.0

Mutations in a voltage-gated sodium channel (SCN1A) result in Dravet Syndrome (DS), a catastrophic childhood epilepsy. Zebrafish with a mutation in scn1Lab recapitulate salient phenotypes associated with DS, including seizures, early fatality, and resistance to antiepileptic drugs. To discover new drug candidates for the treatment of DS, we screened a chemical library of ∼1000 compounds and identified 4 compounds that rescued the behavioral seizure component, including 1 compound (dimethadione) that suppressed associated electrographic seizure activity. Fenfluramine, but not huperzine A, also showed antiepileptic activity in our zebrafish assays. The effectiveness of compounds that block neuronal calcium current (dimethadione) or enhance serotonin signaling (fenfluramine) in our zebrafish model suggests that these may be important therapeutic targets in patients with DS. Over 150 compounds resulting in fatality were also identified. We conclude that the combination of behavioral and electrophysiological assays provide a convenient, sensitive, and rapid basis for phenotype-based drug screening in zebrafish mimicking a genetic form of epilepsy.

Abstract licence: CC BY

Gamma-hydroxybutyrate (GHB), an endogenous compound related to the neurotransmitter gamma-aminobutyric acid (GABA), is used as a therapeutic and recreational drug and as a "weapon" in drug-facilitated crimes. The very short window of detection of GHB in conventional matrices (blood and urine) makes necessary the use of alternative matrices like hair. Hair has a long window of detection and the possibility to perform segmental analysis, which makes it very useful for proving GHB intake. In the present work, a method for quantification of GHB in hair was developed and validated. Hair (10 mg) was washed twice with dichloromethane and then incubated at room temperature with Milli-Q water in an ultrasound bath for 30 min. Analysis was performed by UPLC-MS/MS using a CORTECS UPLC HILIC (1.6 μm), 2.1 × 100-mm column, and a gradient with acetonitrile and ammonium acetate (10 mM) at pH 6.0, with a total run-time of 10 min. For detection, a triple quadrupole mass spectrometer in ESI negative mode was used. The method was validated, following the criteria established in the "AAFS Standard Practices for Method Validation in Forensic Toxicology" guideline, obtaining satisfactory results for linearity (0.5-50 ng/mg), accuracy (95.0%-103.2%), imprecision ( 86.4%), process efficiency (> 46.1%), and autosampler stability (< 4.3%). The method was used for the analysis of 26 authentic hair samples, 25 from non-drug users, obtaining values between < LOQ and 6.25 ng/mg of endogenous GHB and 1 from a former GHB chronic user to prove abstinence.

Abstract licence: CC BY

Sodium oxybate is a newly approved oral treatment for narcolepsy-related cataplexy and excessive daytime sleepiness. It has been misused recreationally and implicated in drug-facilitated crimes. In this study, a highly sensitive and environmentally benign quenching spectrofluorimetric method was established for the quantification of sodium oxybate in both pharmaceutical and spiked plasma matrices. Carbon quantum dots were used as a sustainable fluorescent probe to quantify sodium oxybate via fluorescence quenching. The surface of the fluorescent probe was modified with a sodium oxybate-tetraphenylborate complex to augment selectivity. Sodium oxybate interacts with chromophore sites on the fluorescent probe, leading to a concentration-dependent reduction in the fluorescence intensity of the probe recorded at 450 nm. The method was validated in accordance with the ICH guidelines and demonstrated a good linearity within a working range of 50-600 ng/mL. The method was shown to be sensitive, with detection and quantitation limits of 14.58 and 44.18 ng/mL, respectively. This method was successfully used to quantify sodium oxybate in pharmaceutical and spiked plasma samples, with no interference. Furthermore, the environmental sustainability of the proposed method was evaluated utilizing the Analytical GREEnness calculator metric, yielding a notably elevated greenness score.

Abstract licence: CC BY-NC-ND