Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics

Journal of Psychopharmacology
Miriam Saiz-RodríguezFrancisco Abad-Santos

Abstract

Agomelatine is an agonist of the melatoninergic receptors used for the treatment of depression. Our aim was to evaluate the effect of genetic polymorphisms in metabolising enzymes and the P-glycoprotein transporter on agomelatine pharmacokinetics and pharmacodynamics. Twenty-eight healthy volunteers receiving a single 25 mg oral dose of agomelatine, were genotyped for nine polymorphisms in cytochrome P450 enzymes ( CYP1A2, CYP2C9 and CYP2C19) and adenosine triphosphate-binding cassette subfamily B member 1 ( ABCB1), by real-time polymerase chain reaction . Agomelatine concentrations were measured by high performance liquid chromatography coupled to a tandem mass spectrometry detector. We calculated a CYP1A2 activity score that was directly correlated with agomelatine pharmacokinetics. Individuals with a decreased enzyme activity (*1C carriers) had a lower clearance and accumulated higher concentrations of agomelatine. In contrast, individuals with a high CYP1A2 inducibility (*1F or *1B carriers) showed an extensive clearance and lower agomelatine concentrations. The apparently marked differences between races were due to the different CYP1A2 genotype distribution. CYP2C9 intermediate/poor metabolisers showed a higher area under...Continue Reading

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May 4, 2018·Basic & Clinical Pharmacology & Toxicology·Miriam Saiz-RodríguezFrancisco Abad-Santos

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Citations

Aug 5, 2020·Pharmacological Reports : PR·Anna HaduchWładysława A Daniel
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Pablo ZubiaurFrancisco Abad-Santos
Apr 23, 2020·Pharmacology & Therapeutics·Eva Gil-MartinsRenata Silva
Apr 4, 2021·Journal of Personalized Medicine·Pablo ZubiaurFrancisco Abad-Santos
May 13, 2021·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·C B EapC Hiemke
May 18, 2021·Frontiers in Pharmacology·Gina Mejía-AbrilFrancisco Abad-Santos
Jun 3, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dongyi SunXin Wang

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Methods Mentioned

BETA
PCR
genotyping

Software Mentioned

WinNonlin
SPSS

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