Corkery, John

de la Torre, R.

Magi, Farré

Olesti, E.

Papaseit, E.

Torrens, Marta

English

University of Hertfordshire Research Archive

E. Papaseit1,  E. Olesti2, R.  de la Torre2, J. Corkery3, M. Torrens4, M. Farré11Hospital Universitari Germans Trias i Pujol, Badalona-IGTP, UAB-IMIM, Badalona, Spain2Hospital del Mar Medical Research Institute-IMIM, UAB and UPF, Barcelona, Spain3Centre for Clinical Practice, Safe Medicines and Drug Misuse Research, Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit, University of Hertfordshire, UK 4Institut de Neuropsiquiatria i Addiccions, Parc de Salut Mar, IMIM. UAB, Barcelona, SpainIntroductionMephedrone (4-methylmethcathinone, 4-MMC) has becomeestablished as a permanent illicit drug in the dynamic newpsychoactive substances (NPS) scene.Objectives and AimsThe aim of this work is to collect published data on themephedrone concentrations in biological samples from cases ofacute intoxications (fatal and non-fatal) and compare with resultsfrom human pharmacokinetics studies, wastewater andanonymous pooled urine analysisMethodsThe PubMed® database complemented with Google Scholar®were systematically searched from database inception untilFebruary 15, 2017, to find published cases of mephedroneintoxications and concentrations in biological samples..Concentrations of mephedrone in cases of fatal and non-fatal clinical intoxicationsResultsOver the studied period, a total of 437 articles were identified forthe general search “mephedrone OR 4-methylmethcathinone”,only publications including specific toxicokinetics criteria wereincluded to review consideration.A total of 97 fatal cases and 57 non-fatal intoxication providingmephedrone concentrations in human biological matrices andattributed directly or indirectly to mephedrone were found.Mephedrone mean blood concentrations from fatal cases were2,663 ng/mL (range 51-22,000 ng/mL), and from non-fatal casesmean were 166 ng/mL (range, 13-412 ng/mL) (Table 1, Table 2).These were in a similar range from data found in controlledstudies of mephedrone pharmacokinetics non reporting acutetoxicity (135 ng/mL, range 52-218 ng/mL) (Table 3). Forensicepidemiology studies based on wastewater and anonymouspooled urine analysis point towards similar variations in use(nightclub scene) to those self-reported in surveys andquestioners.ConclusionsMephedrone blood concentrations in cases of fatal intoxications were higher than in non-fatal cases. In both, great variability inmephedrone concentration were found that could be explained by interindividual differences in pharmacokinetics-pharmacodynamics, dose and routes of administration and concomitant poly-drug use.AcknowledgementsSubjects Oral dose (mg)  Blood (ng/mL) Setting Clinical findingsN=12 200 135 Clinical Trial Unit Prototypical acute effects/ Method validationN=12 200 159 N=6 150 123 N= 3 100 22 N= 3 50  42 SubjectsBlood Clinical presentationMephedrone(ng/mL)Other drugsN=1 500 ND UnresponsiveN=1 22000 Diazepam, nordiazepam,amphetamineMethod validationN=1 3300 NTN=1 5700 NTN=1 1200 NTN=1 980 (femoral) Atropine, naloxone, CollapsedN=1 2240 (femoral) Atropine, 3-TFMPP Shake and twitch, sweaty and acting strangelyN=1 130 (femoral) Methadone, diazepam, nordiazepam,olanzepine, chlorpromazine metaboliteUnresponsiveN=1 230 (femoral) NR Traffic collisionN=1 51  NR Metabolism studyN=1 5100(femoral) Cocaine, benzoylecgonine,methylecgonine, MDMA, oxazepam,midazolamFuryN=42 1483 (10-22.000) Positive /negative NPSAD data recordN=1 500 (blood heart post-mortem)GHB (blood heart  post-mortem) UnconsciousnessN=12 160 (3-650) Positive Sudden deathN=1 5500 NT Critical stateN=1 1300 Methcathinone, ethanol No signs of lifeN=1 1330 Ethanol, cocaethylene Found deathN=1 2600 Methylone Death in bedN=1 692 Pentedrone DeathN=1 200 Heroin, butylone, venlaflaxine, zopiclone, diazepam, quetiapineCardiorespiratory arrestN=21 720 Positive/negative NPSAD, EU-MADNESS data record (incomplete)N=1 -- Alpha-PVP Found death (carbon monoxidetoxication)Supported by grants from Instituto de Salud Carlos III (PIS-FEDER PI11/01961; Red de Trastornos Adictivos-RTA-FEDER RD16/0017/0003 and RD16/0017/0010; Juan Rodes fellowship JR16/00020) and The European Commission (HOME/2014/JDRU/AG/DRUG/7082, PREDICT Project).  This paper has been accepted for publication (Curr Pharm Des. 2017 Jul 4. )SubjectsBlood Clinical presentationMephedrone(ng/mL)Other drugs N=1 150 Negative Palpitations, blurred tunnel vision, chest pressure, sweating, unwell feelingN=1 193 THC, 11-OH-THC, 11-nor-9-carboxy-THCUnconsciousnessN= 1 NR NR Method validationN=10 NR NR Method validationN=32 210 (10-740) Negative/Positive Agitation, hyperactivity, twitching  movements, sweat and chew the inside of cheeks, no eye contact, lack of coordination, slurred speech, field impairment tests  test failed…Appearance of  highly intoxicatedN=1 39 Diazepam, nordiazepam, temazepam Unsteady on feet, dilated pupils, drunkenness, slow speechN=1 40 None Slumped across steering wheel, drooling,difficult to wake, dilated pupilsN=1 56  THC Thirst, drowsiness and hyperactivityN=1 110  MDA, MDMA, cocaine, THC Drowsiness, thirst, hyperactivityN=1 350  None Dilated pupilsN=1 MDMA Chewing gums, twitchy, fidgety, dilatedpupils, hyperactivity, thirstN=1  412 THC ,11-OH-THC, THCCOOH,amphetamineDelayed reaction time, deranged sensation of time, deficiency in concentration and pupil abnormalitiesN=1 NT NT Method validationN=1 NT NRN=1 52 THC, THCCOOH Talkative, accelerated heart rate and sluggish pupil reaction to lightN=1 13 3-MMC NRN=1 NR NR Delirious, tachycardiaTable 1. Mephedrone concentrations in human biological samples from fatal cases Table 2. Mephedrone concentrations in human biological samples from non-fatal cases NR: not reportedNT: not testedTable 3. Mephedrone concentrations in human biological samples (clinical trial)NR: not reportedNT: not tested

Concentrations of mephedrone in cases of fatal and non-fatal clinical intoxications

http://uhra.herts.ac.uk/bitstream/2299/27014/1/Poster_NPS_18102017.pdf

Concentrations of mephedrone in cases of fatal and non-fatal clinical intoxications

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