title: Effect of the allelic variants of ABCB1, CYP2D6 and HTR3B on response of ramosetron to prevent chemotherapy-induced nausea and vomiting in Korean cancer patients.
abstract: OBJECTIVE
  Despite appropriate use of antiemetics including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, chemotherapy-induced nausea and vomiting (CINV) is still an unsolved problem in patients with anticancer drugs. We examined whether the variants of ABCB1, CYP2D6 and HTR3B affect efficacy of ramosetron, a selective 5-HT3receptor antagonist in a dose escalation clinical trial.
  
  
  METHODS
  We conducted a clinical trial on patients who underwent FOLFOX combination chemotherapy. The participants were randomized into three groups of ramosetron: 0.3 mg (standard dose), 0.45 mg and 0.6 mg. Rhodes index of nausea, vomiting and retching were measured at 1, 6 h, day 1, day 2 and day 7 after the administration of ramosetron as a clinical parameter of CINV and polymorphism was analyzed from genomic DNA.
  
  
  RESULTS
  There was a dose-dependent decrease in the nausea and vomiting scores at day 1 and day 2, not statistically significant. The Rhodes index of nausea, vomiting and retching score at day 1 in participants with HTR3B-100_-102delAAG deletion variants was significantly higher than wild type participants, regardless of dosages. However, the polymorphisms including ABCB1, CYP2D6 and other HTR3B genes did not affect response to ramosetron after chemotherapy.
  
  
  CONCLUSIONS
  These results suggest that the -AAG deletion variant of the 5-HT3Breceptor gene may contribute to variability in response to antiemetic therapy for CINV regardless of dose escalation. These results suggest that carrying a -100_-102delAAG variant of 5-HT3gene should be supported by alternate or additive antiemetics in addition to 5-HT3antagonists to control acute emesis.
authors.affiliation: Division of Clinical Pharmacology, Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Gaeun
authors.initials: G
authors.lastname: Kang
authors.affiliation: Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ka-Rham
authors.initials: KR
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Shim
authors.affiliation: Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jun-Eul
authors.initials: JE
authors.lastname: Hwang
authors.affiliation: Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Woo-Kyun
authors.initials: WK
authors.lastname: Bae
authors.affiliation: Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.affiliation: Department of Preventive Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Hee-Nam
authors.initials: HN
authors.lastname: Kim
authors.affiliation: PIPET (Pharmacometrics Institute for Practical Education and Training), Seoul, Korea.
authors.forename: Jongtae
authors.initials: J
authors.lastname: Lee
authors.affiliation: PIPET (Pharmacometrics Institute for Practical Education and Training), Seoul, Korea.|Division of Mathematics, College of Science and Technology, Hongik University at Sejong, Jochiwon, Chungnam, Korea.
authors.forename: Kyungmee
authors.initials: K
authors.lastname: Choi
authors.affiliation: Division of Clinical Pharmacology, Chonnam National University Hospital, Gwangju, Korea.|Department of Biomedical Science, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Division of Clinical Pharmacology, Chonnam National University Hospital, Gwangju, Korea.|Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Division of Clinical Pharmacology, Chonnam National University Hospital, Gwangju, Korea.|Department of Anethesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Cho
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D001562:Benzimidazoles / Q000008:administration & dosage*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D014839:Vomiting / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000932:Antiemetics; D000970:Antineoplastic Agents; D001562:Benzimidazoles; C509410:HTR3B protein, human; D044406:Receptors, Serotonin, 5-HT3; C071315:ramosetron; D019389:Cytochrome P-450 CYP2D6
keywords: chemotherapy; nausea; polymorphism; ramosetron; vomiting