Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients.
Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients.
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遗传和非遗传因素对羟考酮治疗的癌症患者对丙氯拉嗪临床反应的影响。
DOI：
10.1016/j.cca.2013.12.011
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kawakami J.
中科院分区：
文献类型：
--
作者：
Tashiro M;Naito T;Ohnishi K;Kagawa Y;Kawakami J.
背景在阿片类药物治疗的患者中，DRD 2和OPRM 1基因变异体对丙氯拉嗪临床反应的贡献仍有待澄清。我们评估了非遗传和遗传因素的基础上，在羟考酮治疗patients.MethodsSeventy日本癌症患者开始口服丙氯拉嗪与羟考酮的临床反应。测定给药前血浆丙氯拉嗪浓度和血清催乳素浓度。羟考酮引起的恶心和呕吐的发生率进行了监测2 weeks. ResultsProchlorperazine血浆浓度和羟考酮每日剂量与恶心和呕吐的发生率无关。DRD 2 TaqIA A1 A2 + A1 A1组恶心发生率显著高于A2 A2组。女性的呕吐发生率明显高于男性。服用丙氯拉嗪前后，女性患者血清催乳素浓度显著高于男性患者。结论DRD 2 TaqIA和女性性别改变了丙氯拉嗪的预防性止吐效果; OPRM 1 A118 G、丙氯拉嗪的血浆暴露量和性别影响了羟考酮治疗患者的催乳素分泌。
BackgroundThe 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.MethodsSeventy 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 2 weeks.ResultsPlasma prochlorperazine concentration and oxycodone daily dose were not associated with the incidences of nausea and vomiting. The incidence of nausea was significantly higher in theDRD2 TaqIA A1A2+A1A1group than in theA2A2group. 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 theOPRM1 118AAgroup than in theAG+GGgroup.ConclusionsDRD2 TaqIAand female gender altered the prophylactic antiemetic efficacy of prochlorperazine.OPRM1 A118Gtogether with plasma exposure of prochlorperazine and gender affected prolactin secretion in oxycodone-treated patients.