title: Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients.
abstract: BACKGROUND
  The contributions of DRD2 and OPRM1 genetic variants to clinical responses to prochlorperazine remain to be clarified in opioid-treated patients. We evaluated the clinical responses to prochlorperazine based on non-genetic and genetic factors in oxycodone-treated patients.
  
  
  METHODS
  Seventy Japanese cancer patients starting oral prochlorperazine together with oxycodone were enrolled. Predose plasma prochlorperazine concentrations and serum prolactin concentrations were determined. The incidences of oxycodone-induced nausea and vomiting were monitored for 2weeks.
  
  
  RESULTS
  Plasma prochlorperazine concentration and oxycodone daily dose were not associated with the incidences of nausea and vomiting. The incidence of nausea was significantly higher in the DRD2 TaqIA A1A2+A1A1 group than in the A2A2 group. The incidence of vomiting was significantly higher in females than in males. Before and after the prochlorperazine administration, the serum prolactin concentration was significantly higher in female patients than in male patients. The serum prolactin concentration was weakly correlated with prochlorperazine concentration and was significantly higher in the OPRM1 118AA group than in the AG+GG group.
  
  
  CONCLUSIONS
  DRD2 TaqIA and female gender altered the prophylactic antiemetic efficacy of prochlorperazine. OPRM1 A118G together with plasma exposure of prochlorperazine and gender affected prolactin secretion in oxycodone-treated patients.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; Department of Clinical Pharmaceutics and Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Shizuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.affiliation: Oncology Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Clinical Pharmaceutics and Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Shizuoka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. Electronic address: kawakami-ham@umin.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D000932:Antiemetics / Q000097:blood / Q000494:pharmacology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D010098:Oxycodone / Q000009:adverse effects* / Q000627:therapeutic use; D011346:Prochlorperazine / Q000097:blood / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000932:Antiemetics; C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D011388:Prolactin; D010098:Oxycodone; D011346:Prochlorperazine
keywords: Cancer patients; DRD2; OPRM1; Oxycodone; Prochlorperazine; dopamine receptor D2; opioid receptor mu 1