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

Pharmacokinetics of Blonanserin and Its Main Metabolite after Multiple-Dose Administration in Chinese Healthy Volunteer

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(4 mg bid组和8 mg qd组),分别连续7 d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60 h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4 mg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,t max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,AUC SS分别为(3 933.00±1 005.96)和(2 404.56±813.03)ng·h·L-1,AUC0-∞分别为(8 160.18±2 173.64)和(7 730.84±1 732.06)ng·h·L-1,8 mg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,t max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,AUC SS分别为(6 956.05±3 372.90)和(5 033.31±1 699.39)ng·h·L-1,AUC0-∞分别为(9 660.33±3 594.69)和(9 377.57±2 686.91)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。

OBJECTIVE To study the pharmaeokinetics 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 hid 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（2404.56 ±813.03） ng · L^-1; AUC0-∞ were（ 8 160. 18 ±2 173. 64） and （7 730. 84 ± 1 732. 06 ）ng · L^-1. CONCLUSION The inter-individual variation of the pharmacokinetic parameters of blonanserin is very large and therapeutic drug monitoring of blonanserin will he needed during clinical therapy.