Seven fatalities associated with ethylphenidate

Abstract

Ethylphenidate is a stimulant novel psychoactive substance that is an analogue of the prescription drug methylphenidate (Ritalin ®. Methylphenidate is used commonly for the treatment of attention deficit hyperactivity disorder. Due to its stimulant effects ethylphenidate is being abused. There is a single case report of a death associated with ethylphenidate in Germany, and a case series of 19 deaths in the East of Scotland, but otherwise, the contribution of ethylphenidate to death is poorly documented. We report the analytical results of 7 cases (between February 2013 and January 2015) in which ethylphenidate was detected and quantitated with a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). The individuals (all male) ranged in age from 23 to 49 years (median 25 years). The concentration of ethylphenidate in the cases ranged from 0.026 mg/L to 2.18 mg/L in unpreserved post-mortem femoral blood. Only one case had ethylphenidate present as a sole drug. All other cases had at least 2 other drug classes present (benzodiazepines, heroin, methadone antipsychotics, other new psychoactive compounds). Ethylphenidate toxicity was the sole contribution to the cause of death in one case. Hanging was the cause of death in 2 cases, with the other 4 cases being reported as having occurred due to mixed drug toxicity. These data will further help with the interpretation of post-mortem ethylphenidate levels.

L‐ and D‐threo ethylphenidate concentrations, pharmacokinetics, and pharmacodynamics in horses

“…Additionally, as this is the first report of EPH administration in horses, a limited dose range was selected for administration and it is possible that higher doses may elicit changes in cardiac parameters as well as stimulatory or excitatory effects. While all reports of EPH intoxication that are described in the literature are post‐mortem, doses eliciting adverse effects are much higher than those used in the current study …”

“…With the exception of 1 horse, the elimination half‐life of EPH in horses (harmonic mean ± SD: 0.395 ± 0.174–1.32 ± 0.442 hours) is slightly shorter than that reported for methylphenidate (2.35 hours). As elimination of both involves biotransformation to ritalinic acid, differences in the elimination half‐life of EPH and methylphenidate is likely attributable to differences in the rate of conversion to ritalinic acid.…”

“…As there are no published reports describing the pharmacodynamic effects of EPH in horses, a secondary goal of the current study was to assess physiological responses following administration. There is currently no approved therapeutic use for this compound, and therefore reports of its effects in other species are limited to those associated with recreational use or cases of intoxication . As the compounds are structurally related with similar mechanism of action, it is likely that the abuse of EPH in horse racing would be for similar reasons as has been reported for methylphenidate, including improvement of performance and demeanor .…”

“…There is no currently approved therapeutic use for EPH; however, it is commonly used as a “recreational drug of abuse.” In addition to direct ingestion, EPH exposure can occur following concurrent ingestion of methylphenidate and alcohol . In humans, EPH exposure reportedly leads to stimulation, euphoria, increased focus, and improved concentration through inhibition of dopamine and norepinephrine reuptake . In humans, there are numerous reports of intoxication following both acute and chronic ingestion .…”

“…In humans, EPH exposure reportedly leads to stimulation, euphoria, increased focus, and improved concentration through inhibition of dopamine and norepinephrine reuptake . In humans, there are numerous reports of intoxication following both acute and chronic ingestion . Adverse effects include chest pain, heart palpitations, agitation, and death .…”