title: Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.
abstract: The fluoropyrimidines are the mainstay chemotherapeutic agents for the treatment of many types of cancers. Detoxifying metabolism of fluoropyrimidines requires dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene), and reduced or absent activity of this enzyme can result in severe, and sometimes fatal, toxicity. We summarize evidence from the published literature supporting this association and provide dosing recommendations for fluoropyrimidines based on DPYD genotype (updates at http://www.pharmgkb.org).
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Caudle
authors.forename: C F
authors.initials: CF
authors.lastname: Thorn
authors.forename: T E
authors.initials: TE
authors.lastname: Klein
authors.forename: J J
authors.initials: JJ
authors.lastname: Swen
authors.forename: H L
authors.initials: HL
authors.lastname: McLeod
authors.forename: R B
authors.initials: RB
authors.lastname: Diasio
authors.forename: M
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D054067:Dihydropyrimidine Dehydrogenase Deficiency / Q000175:diagnosis / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D005838:Genotype; D006801:Humans; D033162:Incidental Findings; D008297:Male; D018570:Risk Assessment; D012737:Sex Factors; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005641:Tegafur; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil