Pharmacogenetic considerations with dichloroacetate dosing.

Abstract:

:The investigational drug dichloroacetate (DCA) is a metabolic regulator that has been successfully used to treat acquired and congenital metabolic diseases and, recently, solid tumors. Its clinical use has revealed challenges in selecting appropriate doses. Chronic administration of DCA leads to inhibition of DCA metabolism and potential accumulation to levels that result in side effects. This is because conversion of DCA to glyoxylate is catalyzed by one enzyme, glutathione transferase zeta 1 (GSTZ1-1), which is inactivated by DCA. SNPs in the GSTZ1 gene result in expression of polymorphic variants of the enzyme that differ in activity and rates of inactivation by DCA under physiological conditions: these properties lead to considerable variation between people in the pharmacokinetics of DCA.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

James MO,Stacpoole PW

doi

10.2217/pgs-2015-0012

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

743-53

issue

7

eissn

1462-2416

issn

1744-8042

journal_volume

17

pub_type

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