title: Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration.
abstract: Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with potentially life-threatening toxicity following the administration of standard doses of 5-fluorouracil. This syndrome derives its importance from the fact that approximately 2 million patients receive the drug worldwide each year. Population studies have suggested that 4%-7% of the American population exhibit dose-limiting toxicity that might be associated with a genetic defect in the DPYD gene that encodes for the DPD enzyme. During the past several years it has become increasingly clear that genetics is a major determinant of the variability in drug response, accounting for the probability of drug efficacy and the likelihood of toxic drug reactions. This article briefly discusses the clinical presentation, laboratory diagnosis, pharmacokinetics, inheritance, and the clinical management options of DPD deficiency. The variability of DPD enzyme activity in population studies and the different DPYD alleles together with new phenotypic and genotypic methods of screening for DPD deficiency will also be reviewed.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham, 35294-3300, USA.
authors.forename: Hany
authors.initials: H
authors.lastname: Ezzeldin
authors.forename: Robert
authors.initials: R
authors.lastname: Diasio
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003937:Diagnosis, Differential; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000494:pharmacology; D005472:Fluorouracil / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D008659:Metabolic Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D013577:Syndrome
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil