石红梅,王占璋,张明,倪晓佳,胡晋卿,邱畅,温预关,尚德为
SHI Hongmei,WANG Zhanzhang,ZHANG Ming,NI Xiaojia,HU Jinqing,QIU Chang,WEN Yuguan,SHANG Dewei

• 1:广州市惠爱医院(广州医科大学附属脑科医院)

摘要(Abstract)：

目的研究中国健康受试者多次服用布南色林后布南色林血药浓度与血清中催乳素水平的量效关系。方法 11名健康受试者(5男,6女)连续服用布南色林6 d,每天早晚给服药1次,每次4 mg,于第7天服药前(0 h)以及服药后0.5、1、2、4、8、12和24 h采集静脉血5 m L,分别测定血浆中布南色林药物浓度和血清中催乳素水平,采用非线性混合效应模型法(NONMEM)对布南色林血药浓度和催乳素水平进行数据拟合,求算药效动力学参数。结果服药2 h后受试者血清中催乳素水平达到峰值,服药60 h后,男性和女性受试者催乳素均恢复至正常水平,男性和女性受试者催乳素变化具有显著差别,男性受试者催乳素变化的Emax约为903 m IU/L,而女受试者催乳素变化的Emax约为男性受试者的2.61倍,EC50值96.3 ng/L。结论布南色林可以引起催乳素显著升高,但不会显著引起催乳素大量蓄积,表明布南色林用药是安全的。
OBJECTIVE To establish the dose-response relationship of palsma blonanserin concentrations and the serum prolactin levels in Chinese healthy volunteers after multi-dose administration. METHODS Eleven volunteers( 5 males,6 females) were administrated blonanserin 4 mg bid continuously for 7 d. Blood samples were collected on day 7 at 0 h( before administration),0.5,1,2,4,8,12 h and 24 h after administration. The levels of prolactin in the serum and blonanserin concentrations in plasma were measured,respectively. Non-linear mixed effect models were used to fit the data and estimate the pharmacodynamic parameters.RESULTS Prolactin serum level reached the peak after 2 h of administration. In both male and female volunteers prolactin concentrations returned to the normal levels 60 h later. The changes of the prolactin level were significantly different between the males and females. The Emaxvalue in the males was 903 m IU / L,while in the females it was 2.61-fold of the males. The EC50 was 96.3 ng / L.CONCLUSION Blonanserin could cause a significant increase of prolactin,while no accumulation of prolactin was observed.Therefore,blonanserin is safe for the clinical use.

关键词(KeyWords)： 布南色林;催乳素;NONMEM;量效关系
blonanserin;prolactin;NONMEM;dose-response relationship

Abstract:

Keywords:

基金项目(Foundation): 广州市医药卫生科技项目(20131A011087;20141A010038);; 广东省医院药学研究基金(奥赛康基金)(2015A09);; 广州市脑科医院广州市医学重点学科建设项目子项目(GBH2014-QN05)

作者(Author): 石红梅,王占璋,张明,倪晓佳,胡晋卿,邱畅,温预关,尚德为
SHI Hongmei,WANG Zhanzhang,ZHANG Ming,NI Xiaojia,HU Jinqing,QIU Chang,WEN Yuguan,SHANG Dewei

参考文献(References)：

• [1]Yang J,Bahk WM,Cho HS,et al.Efficacy and tolerability of Blonanserin in the patients with schizophrenia:a randomized,double-blind,risperidone-compared trial[J].Clin Neuropharmacol,2010,33(4):169-175.
• [2]常麦会,李乐华.新型抗精神病药:布南色林[J].中国新药与临床杂志,2010,29(8):571-575.
• [3]Deeks ED,Keeting GM.Blonanserin:a review of its use in the management of schizophrenia[J].CNS Drugs,2010,24(4):65-84.
• [4]Wen YG,Ni XJ,Zhong M,et al.Simultaneous determination of blonanserin and its metabolite in human plasma and urine by liquid chromatography-tandem mass spectrometry:application to a pharmacokinetic study[J].J Chromatogr B Analyt Technol Biomed Life Sci,2012,903:46-52.
• [5]尚德为,陈庆强,谭焕君,等.布南色林及其代谢产物在中国健康受试者的多剂量药代动力学[J].中国药学杂志,2013,48(15):1308-1311.
• [6]石红梅,黄顺燕,温光池,等.新型抗精神分裂症药布南色林对催乳素的影响[J].今日药学,2013,23(12):783-784.
• [7]Tenjin T,Miyamoto S,Ninomiya Y,et al.Profile of blonanserin for the treatment of schizophrenia[J].Neuropsychiatr Dis Treat,2013,9:587-594.
• [8]Lonasen(blonanserin)[product information].2009.Dainippon Sumitomo Pharma Corp,Japan.(in Japanese).