title: Toxicity evaluation of α-pyrrolidinovalerophenone (α-PVP): results from intoxication cases within the STRIDA project.
abstract: BACKGROUND
  An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving the stimulant NPS α-pyrrolidinovalerophenone (α-PVP), a potent dopamine re-uptake inhibitor, over a 4-year period.
  
  
  METHODS
  Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from 2012 to 2015.
  
  
  METHODS
  In the STRIDA project, blood and urine samples are collected from intoxicated patients with admitted or suspected intake of NPS or unknown drugs presenting to hospitals over the country. Analysis of NPS is performed by mass spectrometry multicomponent methods. Clinical data are collected when caregivers consult the Swedish Poisons Information Centre (PIC), and retrieved from medical records. The severity of poisoning is graded retrospectively using the Poisoning Severity Score (PSS). The inclusion criteria for this study included absence of other stimulants than α-PVP.
  
  
  RESULTS
  During the 4-year study period, 23 intoxications were originally coded as "α-PVP related" out of a total 3743 NPS-related inquiries (0.6%) at the PIC. The present study covered 42 analytically confirmed cases in which α-PVP was the only stimulant detected. The age range of patients was 20-58 (median 32) years, of which 79% were males. The α-PVP concentration in serum was 4.0-606 (median 64; n = 42) ng/mL and 2.0-41,294 (median 1782; n = 25) ng/mL in urine. There was no statistically significant association between the serum α-PVP concentration and urinary α-PVP/creatinine ratio in 25 cases, where both sets of data were available. In 14/42 (33%) cases, α-PVP was the only psychoactive substance identified. In the remaining cases, additional substances comprised opioids, benzodiazepines, and ethanol. The main clinical manifestations were tachycardia (80%), agitation (70%), hypertension (33%), hallucinations (20%), and delirium (18%). Classification of poisoning severity yielded 25 (60%) moderate (PSS 2), 7 (17%) severe (PSS 3), and 2 fatal cases (PSS 4).
  
  
  CONCLUSIONS
  In analytically confirmed α-PVP intoxication cases involving no other stimulant drugs, the urine and serum concentrations showed high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results further demonstrated that α-PVP prevailed as a drug of abuse after being classified as a narcotic substance, and despite a high incidence of severe poisonings and fatalities. However, the low prevalence of α-PVP cases registered at the PIC suggested that many were unaware of the actual substance they had taken.
authors.affiliation: a Department of Laboratory Medicine , Karolinska Institutet , Stockholm , Sweden ;|b Department of Clinical Pharmacology , Karolinska University Laboratory , Stockholm , Sweden ;
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
authors.affiliation: c Swedish Poisons Information Centre , Stockholm , Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Franzén
authors.affiliation: c Swedish Poisons Information Centre , Stockholm , Sweden.
authors.forename: Matilda
authors.initials: M
authors.lastname: Bäckberg
authors.affiliation: b Department of Clinical Pharmacology , Karolinska University Laboratory , Stockholm , Sweden ;
authors.forename: Patrick
authors.initials: P
authors.lastname: Signell
authors.affiliation: a Department of Laboratory Medicine , Karolinska Institutet , Stockholm , Sweden ;|b Department of Clinical Pharmacology , Karolinska University Laboratory , Stockholm , Sweden ;
authors.forename: Anders
authors.initials: A
authors.lastname: Helander
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000506:poisoning / Q000652:urine; D001569:Benzodiazepines / Q000097:blood / Q000506:poisoning / Q000652:urine; D000697:Central Nervous System Stimulants / Q000097:blood / Q000506:poisoning* / Q000652:urine; D003404:Creatinine / Q000652:urine; D003693:Delirium / Q000139:chemically induced / Q000175:diagnosis; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000506:poisoning / Q000652:urine; D000431:Ethanol / Q000097:blood / Q000506:poisoning / Q000652:urine; D005260:Female; D006212:Hallucinations / Q000139:chemically induced / Q000175:diagnosis; D006760:Hospitalization; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000175:diagnosis; D013287:Illicit Drugs / Q000097:blood / Q000506:poisoning* / Q000652:urine; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000209:etiology; D011759:Pyrrolidines / Q000097:blood / Q000506:poisoning* / Q000652:urine; D012189:Retrospective Studies; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000209:etiology; D013548:Sweden; D013610:Tachycardia / Q000139:chemically induced / Q000175:diagnosis; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D013287:Illicit Drugs; D011759:Pyrrolidines; C542924:alpha-pyrrolidinovalerophenone; D001569:Benzodiazepines; D000431:Ethanol; D003404:Creatinine
keywords: Alpha-PVP; illicit drugs; intoxications; liquid chromatography-mass spectrometry; new psychoactive substances