Dose-response pharmacological study of mephedrone and its metabolites: pharmacokinetics, serotoninergic effects, and impact of CYP2D6 genetic variation

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dc.contributor.author	Olesti Muñoz, Eulàlia
dc.contributor.author	Farré Albaladejo, Magí
dc.contributor.author	Carbó Banús, Marcel·lí
dc.contributor.author	Papaseit Fontanet, Esther
dc.contributor.author	Pérez Mañá, Clara
dc.contributor.author	Torrens, Marta
dc.contributor.author	Yubero Lahoz, Samanta, 1985-
dc.contributor.author	Pujadas Bastardes, Mitona
dc.contributor.author	Pozo Mendoza, Óscar J., 1975-
dc.contributor.author	Torre Fornell, Rafael de la
dc.date	2019
dc.identifier.citation	Olesti E, Farré M, Carbó ML, Papaseit E, Perez-Mañá C, Torrens M. et al. Dose-response pharmacological study of mephedrone and its metabolites: pharmacokinetics, serotoninergic effects, and impact of CYP2D6 genetic variation. Clin Pharmacol Ther. 2019 Sep;106(3):596-604. DOI 10.1002/cpt.1417
dc.identifier.citation	0009-9236
dc.identifier.citation	http://dx.doi.org/10.1002/cpt.1417
dc.identifier.uri	http://hdl.handle.net/10230/43021
dc.format	application/pdf
dc.language.iso	eng
dc.publisher	Wiley
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.rights	This is the peer reviewed version of the following article: Olesti E, Farré M, Carbó ML, Papaseit E, Perez-Mañá C, Torrens M. et al. Dose-response pharmacological study of mephedrone and its metabolites: pharmacokinetics, serotoninergic effects, and impact of CYP2D6 genetic variation. Clin Pharmacol Ther. 2019 Sep;106(3):596-604. which has been published in final form at http://dx.doi.org/10.1002/cpt.1417. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
dc.subject	Medicaments -- Administració
dc.subject	Medicaments -- Toxicologia
dc.subject	Mephedrone
dc.title	Dose-response pharmacological study of mephedrone and its metabolites: pharmacokinetics, serotoninergic effects, and impact of CYP2D6 genetic variation
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/acceptedVersion
dc.description.abstract	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 CYP2D6 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 CYP2D6 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 CYP2D6. Mephedrone pharmacology presented a linear dose-dependence within the range of doses tested. The metabolism of mephedrone by CYP2D6 implies that recreational users with no or low CYP2D6 functionality are exposed to unwanted acute toxicity episodes.

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