Enantiospecific pharmacogenomics of fluvastatin

Show full item record




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 organization: INDIVIDRUG - Individualized Drug Therapy
Department of Clinical Pharmacology
Divisions of Faculty of Pharmacy
Drug Delivery Unit
Division of Pharmaceutical Biosciences
Drug Research Program
Janne Backman / Principal Investigator
Date: 2019-09
Language: eng
Number of pages: 13
Belongs to series: Clinical Pharmacology and Therapeutics
ISSN: 0009-9236
DOI: https://doi.org/10.1002/cpt.1463
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
genotype score
massive parallel sequencing
next generation sequencing
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
cpt.1463.pdf 761.9Kb PDF View/Open
Enantiospecific ... enomics_of_fluvastatin.pdf 1.335Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record