CCC v4n3

Submitted: Apr 9, 2004; Revised: Jul 19, 2004; Accepted: Jul 19, 2004 Address for correspondence: Robert Diasio, MD, University of Alabama at Birmingham, Department of Pharmacology and Toxicology and UAB Comprehensive Cancer Center, 1824 6th Ave S, Wallace Tumor Institute, Room 620, University of Alabama at Birmingham, Birmingham, AL 35294-3300 Fax: 205-975-5650; e-mail: [email protected] Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham Hany Ezzeldin, Robert Diasio Review Comprehensive Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with potentially lifethreatening 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. Clinical Colorectal Cancer, Vol. 4, No. 3, 181-189, 2004