Premium
Dose‐Response Pharmacological Study of Mephedrone and Its Metabolites: Pharmacokinetics, Serotoninergic Effects, and Impact of CYP2D6 Genetic Variation
Author(s) -
Olesti Eulàlia,
Farré Magí,
Carbó Marcel·lí,
Papaseit Esther,
PerezMañá Clara,
Torrens Marta,
YuberoLahoz Samanta,
Pujadas Mitona,
Pozo Óscar J.,
Torre Rafael
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1417
Subject(s) - mephedrone , pharmacology , cyp2d6 , pharmacokinetics , toxicity , crossover study , medicine , cytochrome p450 , drug , metabolism , placebo , alternative medicine , pathology
Mephedrone (MEPH), the most widely consumed synthetic cathinone, has been associated with acute toxicity episodes. The aim of this report was to study its metabolic disposition and the impact of genetic variation of CYP 2D6 on MEPH metabolism, in a dose range compatible with its recreational use. A randomized, crossover, phase I clinical trial was performed. Subjects received 50 and 100 mg ( n = 3) and 150 and 200 mg ( n = 6) of mephedrone and were genetically and phenotypically characterized for the CYP 2D6 allelic variation. Our results showed a linear kinetics of mephedrone at the dose range assayed: plasma concentrations, cardiovascular and subjective effects, and blood serotonin concentrations all correlated in a dose‐dependent manner. Mephedrone metabolic disposition is mediated by CYP 2D6 . Mephedrone pharmacology presented a linear dose‐dependence within the range of doses tested. The metabolism of mephedrone by CYP 2D6 implies that recreational users with no or low CYP 2D6 functionality are exposed to unwanted acute toxicity episodes.