Strategies for Avoiding Benzopyrone Hepatotoxicity in Lymphedema Management-The Role of Pharmacogenetics, Metabolic Enzyme Gene Identification, and Patient Selection

Lymphatic Research and Biology
Minhao Hu, Neil Piller

Abstract

Benzopyrones are plant-derived chemicals which have an evidenced degree of clinical efficacy in lymphedema management indicated in past trials. Unfortunately, in some of these cases idiosyncratic hepatotoxicity have been documented in a minority of patients. This review aims to tackle the problem of benzopyrone (particularly coumarin) toxicity by considering their metabolic pathways and identifying relevant alleles needed to take a targeted pharmacogenetic approach in its future use. The nontoxic 7-hydroxylation and the toxic heterocyclic "ring-splitting" epoxidation pathways are the two main detoxification pathways in the hepatometabolism of coumarin, the former catalyzed by CYP2A6 and the latter by possibly CYP1A and CYP2E. Acetaldehyde dehydrogenase (ALDH) clears toxic aldehyde intermediates. CYP2A6 polymorphism screening methods, including genotyping, by real-time polymerase chain reaction and chromatography-mass spectroscopy functional metabolite assays; efficiency of these techniques are continually improving. ALDH polymorphisms have also been implicated, with clinically viable screening tests, rapid genotyping, and sensitive questionnaires already available for ALDH2*1/ALDH2*2. Dysfunctional polymorphisms of the above ge...Continue Reading

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Citations

Mar 28, 2019·Expert Review of Clinical Pharmacology·Ramón CacabelosJuan C Carril

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Methods Mentioned

BETA
genotyping
electrophoresis

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