目的研究布南色林及其代谢产物在中国健康受试者多剂量药动学特征。方法20名健康受试者随机分成两组(4mgbid组和8mgqd组)，分别连续7d口服布南色林，采集第5、6、7日早晨服药前和第7日服药后60h内血样;采用HPLC-MS/MS测定血浆中布南色林及其主要代谢产物N-去乙基布南色林的浓度，并采用DAS程序对试验数据进行处理，计算药动学参数。结果4mg组布南色林及其代谢物的药动学参数ρav分别为(327.75±83.83)和(200.38±67.75)ng·L-1，tmax分别为(1.48±0.69)和(4.15±2.16)h，t1/2分别为(12.98±3.35)和(18.68±4.90)h，AUCSS分别为(3933.00±1005.96)和(2404.56±813.03)ng·h·L-1，AUC0-∞分别为(8160.18±2173.64)和(7730.84±1732.06)ng·h·L-1，8mg组布南色林及其代谢物的药动学参数分别为(289.84±140.54)和(209.72±70.81)ng·L-1，tmax分别为(1.63±0.87)和(3.80±1.03)h，t1/2分别为(15.90±5.12)和(19.70±5.90)h，AUCSS分别为(6956.05±3372.90)和(5033.31±1699.39)ng·h·L-1，AUC0-∞分别为(9660.33±3594.69)和(9377.57±2686.91)ng·h·L-1。结论布南色林药动学参数个体差异较大，需要进行治疗药物监测。
Abstract
OBJECTIVE To study the pharmacokinetics of blonanserin and its main metabolite in Chinese healthy volunteers after multiple-dose administration. METHODS Twenty Chinese healthy volunteers were randomly divided to two groups and given 4 mg blonanserin twice daily(bid) and 8 mg blonanserin once daily(qd) for 7 d,respectively. HPLC-MS/MS was used to determine the plasma concentrations of blonanserin and its metabolite N-desethyl blonanserin. The pharmacokinetic parameters were calculated by DAS software. RESULTS The main pharmacokinetic parameters of blonanserin and its metabolite after multiple-dose administration of 4 mg bid were as follows: ρav were(327.75±83.83) and(200.38±67.75) ng·L-1; tmax were(1.48±0.69) and(4.15±2.16) h; t1/2 were(12.98±3.35) and(18.68±4.90) h; AUCss were(3 933.00±1 005.96) and(2 404.56±813.03) ng·h·L-1; AUC0-∞ were(8 160.18±2 173.64) and(7 730.84±1 732.06) ng·h·L-1. CONCLUSION The inter-individual variation of the pharmacokinetic parameters of blonanserin is very large and therapeutic drug monitoring of blonanserin will be needed during clinical therapy.
关键词
布南色林 /
代谢产物 /
N-去乙基化布南色林 /
高效液相色谱-质谱联用 /
药动学
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Key words
blonanserin /
metabolite /
N-desethyl blonanserin /
LC-MS/MS /
pharmacokinetics
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中图分类号：
R969.1
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参考文献
OHNO Y,OKANO M,IMAKI J,et al.Atypical antipsychotic properties of blonanserin,a novel dopamine D2 and 5-HT2A antagonist.Pharmacol Biochem Behav,2010,96(2):175-180. CHANG M,LI L.A new antipsychotic agent: Blonanserin.Chin J New Drugs Clin Rem(中国新药与临床杂志),2010,29(8): 571-575. GARCIA E,ROBERT M,PERIS F,et al.The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: A randomized,double-blind,placebo-controlled,multicentre study.CNS Drugs,2009,23(7):615-625. DEEKS E D,KEATING G M.Blonanserin: a review of its use in the management of schizophrenia.CNS Drugs,2010,24(1):65-84. YANG J,BAHK W M,CHO H S,et al.Efficacy and tolerability of Blonanserin in the patients with schizophrenia: A randomized,double-blind,risperidone-compared trial.Clin Neuropharmacol,2010,33(4):169-175. ZHOU L Y,ZUO X C,ZHANG B K,et al.Effect of long-term monotherapy of atypical antipsychotics on the levels of body mass index,leptin concentration and insulin resistance in patients with schizophrenia.Chin Pharm J (中国药学杂志),2012,47(12): 997-1000. DU B,ZHAO D G.The safety evaluation of ziprasidone and olanzapine in the treatment of schizophrenia.Chin Pharm J (中国药学杂志),2011,46(13): 1046-1048. SUZUKI H,GEN K.The relationship between the plasma concentration of blonanserin,and its plasma anti-serotonin 5-HT(2A) activity/anti-dopamine D(2) activity ratio and drug-induced extrapyramidal symptoms.Psychiatry Clin Neurosci,2012,66(2):146-152. SARUWATARI J,YASUI-FURUKORI N,INOUE Y,et al.Effect of dose timing in relation to food intake on systemic exposure to blonanserin.Eur J Clin Pharmacol,2010,66(9):899-902.
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脚注
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基金
广东省重大科技专项资助项目(2011A080300003,2012A080204017)；广东省科技厅资助项目(00498500130062027)；广东省药学会资助项目(2012A02)
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