Human pharmacogenomic variations and their implications for antifungal efficacy

Joseph Meletiadis, Stephen Chanock, Thomas J. Walsh

Research output: Contribution to journalReview articlepeer-review

Abstract

Pharmacogenomics is defined as the study of the impacts of heritable traits on pharmacology and toxicology. Candidate genes with potential pharmacogenomic importance include drug transporters involved in absorption and excretion, phase I enzymes (e.g., cytochrome P450-dependent mixed-function oxidases) and phase II enzymes (e.g., glucuronosyltransferases) contributing to metabolism, and those molecules (e.g., albumin, A1-acid glycoprotein, and lipoproteins) involved in the distribution of antifungal compounds. By using the tools of population genetics to define interindividual differences in drug absorption, distribution, metabolism, and excretion, pharmacogenomic models for genetic variations in antifungal pharmacokinetics can be derived. Pharmacogenomic factors may become especially important in the treatment of immunocompromised patients or those with persistent or refractory mycoses that cannot be explained by elevated MICs and where rational dosage optimization of the antifungal agent may be particularly critical. Pharmacogenomics has the potential to shift the paradigm of therapy and to improve the selection of antifungal compounds and adjustment of dosage based upon individual variations in drug absorption, metabolism, and excretion.

Original languageEnglish (US)
Pages (from-to)763-787
Number of pages25
JournalClinical Microbiology Reviews
Volume19
Issue number4
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Epidemiology
  • Immunology and Microbiology(all)
  • Public Health, Environmental and Occupational Health
  • Microbiology (medical)
  • Infectious Diseases

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