title: Does pharmacogenomics account for variability in control of acute chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists?
abstract: Chemotherapy-induced nausea and vomiting is one of the most concerning adverse drug effects from cytotoxic chemotherapy. Despite appropriate use of antiemetic guidelines, 20-30 % of patients experience breakthrough nausea and vomiting secondary to chemotherapy. To assess the variability of 5-hydroxytryptamine type 3 receptor antagonist efficacy caused by genetic variation, a review of the available literature was conducted. From the literature, three sources of pharmacogenomic variability were identified: polymorphisms associated with 5-hydroxytryptamine type 3 receptor subunits, drug metabolism via cytochromes P450, and drug transport in the body. Testing for receptor subunit polymorphisms is not applicable to a clinical setting at this time; however, cytochrome P450 2D6 testing is FDA-approved and widely accessible. Cytochrome P450 2D6 ultrarapid metabolizers and poor metabolizers displayed altered antiemetic efficacy when compared with intermediate metabolizers and extensive metabolizers. We postulate that testing for cytochrome P450 2D6 phenotypes may be the most accessible way to provide individualized antiemetic therapy in the future.
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina, Campus Box 7355, Chapel Hill, NC, 27599-7355, USA. matramme@email.unc.edu
authors.forename: Morgan
authors.initials: M
authors.lastname: Trammel
authors.forename: Mary
authors.initials: M
authors.lastname: Roederer
authors.forename: Jai
authors.initials: J
authors.lastname: Patel
authors.forename: Howard
authors.initials: H
authors.lastname: McLeod
mesh_terms: D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000009:adverse effects*; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D058831:Serotonin 5-HT3 Receptor Antagonists; D019389:Cytochrome P-450 CYP2D6