Enantiospecific pharmacogenomics of fluvastatin

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Hirvensalo , P , Tornio , A , Neuvonen , M , Kiander , W , Kidron , H , Paile-Hyvärinen , M , Tapaninen , T , Backman , J T & Niemi , M 2019 , ' Enantiospecific pharmacogenomics of fluvastatin ' , Clinical Pharmacology and Therapeutics , vol. 106 , no. 3 , pp. 668-680 . https://doi.org/10.1002/cpt.1463

Title: Enantiospecific pharmacogenomics of fluvastatin
Author: Hirvensalo, Päivi; Tornio, Aleksi; Neuvonen, Mikko; Kiander, Wilma; Kidron, Heidi; Paile-Hyvärinen, Maria; Tapaninen, Tuija; Backman, Janne T.; Niemi, Mikko
Contributor: University of Helsinki, INDIVIDRUG - Individualized Drug Therapy
University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
Date: 2019-09
Language: eng
Number of pages: 13
Belongs to series: Clinical Pharmacology and Therapeutics
ISSN: 0009-9236
URI: http://hdl.handle.net/10138/304907
Abstract: Abstract The aim of this study was to investigate how variability in multiple genes related to pharmacokinetics affects fluvastatin exposure. We determined fluvastatin enantiomer pharmacokinetics and sequenced 379 pharmacokinetic genes in 200 healthy volunteers. CYP2C9*3 associated with significantly increased area under the plasma concentration-time curve (AUC) of both 3R,5S- and 3S,5R-fluvastatin (by 67% and 94% per variant allele copy, P = 3.77 ? 10-9 and P = 3.19 ? 10-12). In contrast, SLCO1B1 c.521T>C associated with increased AUC of active 3R,5S-fluvastatin only (by 34% per variant allele copy; P = 8.15 ? 10-8). A candidate gene analysis suggested that CYP2C9*2 also affects the AUC of both fluvastatin enantiomers and that SLCO2B1 single nucleotide variations (SNVs) may affect the AUC of 3S,5R-fluvastatin. Thus, SLCO transporters have enantiospecific effects on fluvastatin pharmacokinetics in humans. Genotyping of both CYP2C9 and SLCO1B1 may be useful in predicting fluvastatin efficacy and myotoxicity. This article is protected by copyright. All rights reserved.
Subject: fluvastatin
CYP2C9
SLCO1B1
pharmacokinetics
pharmacogenomics
genotype score
massive parallel sequencing
next generation sequencing
317 Pharmacy
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