Pharmacogenomics of chloroquine and hydroxychloroquine: current evidence and future implications

Author:

Biswas Mohitosh123ORCID,Sukasem Chonlaphat23456ORCID

Affiliation:

1. Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh

2. Division of Pharmacogenomics & Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand

3. Laboratory for Pharmacogenomics, Ramathibodi Hospital, Somdech Phra Debaratana Medical Center SDMC, Bangkok, 10400, Thailand

4. Pharmacogenomics & Precision Medicine Clinic, Bumrungrad Genomic Medicine Institute (BGMI), Bumrungrad International Hospital, 10110, Bangkok, Thailand

5. Faculty of Pharmaceutical Sciences, Burapha University, Saensuk, Mueang, Chonburi, 20131, Thailand

6. MRC Centre for Drug Safety Science, Department of Pharmacology & Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, L69 3GL, UK

Abstract

As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine’s (CQ) and hydroxychloroquine’s (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some CYP3A5, CYP2D6 and CYP2C8 genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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