Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients

• Published in: Clinica chimica acta Vol. 429; pp. 175 - 180
• Main Authors: Tashiro, Masaki, Naito, Takafumi, Ohnishi, Kazunori, Kagawa, Yoshiyuki, Kawakami, Junichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2014
• Subjects: Aged; Antiemetics - blood; Antiemetics - pharmacology; Cancer patients; DRD2; Female; Genetic Variation; Humans; Male; Middle Aged; Multivariate Analysis; Nausea - chemically induced; Nausea - prevention & control; Neoplasms - blood; Neoplasms - drug therapy; Neoplasms - genetics; OPRM1; Oxycodone; Oxycodone - adverse effects; Oxycodone - therapeutic use; Prochlorperazine; Prochlorperazine - blood; Prochlorperazine - pharmacology; Prolactin - blood; Receptors, Dopamine D2 - genetics; Treatment Outcome; Cancer patients; OPRM1; DRD2; Prochlorperazine; Oxycodone; dopamine receptor D2; opioid receptor mu 1
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2013.12.011

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. 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. 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. 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. •We evaluated the factors related to clinical responses to prochlorperazine.•A higher incidence of nausea was observed in patients with DRD2 TaqIA A1.•Female gender altered the incidence of vomiting.•Plasma exposure of prochlorperazine affected serum prolactin concentration.•Patients with OPRM1 118A had a higher serum prolactin concentration.