进食对健康受试者口服布南色林片药动学特征的影响

Effect of food on pharmacokinetics of single dose of blonanserin tablets in healthy volunteers

目的探讨进食对布南色林在中国健康人群中药动学特征的影响程度。方法本研究采用开放、随机的双周期自身交叉设计。20名男性健康志愿者,随机均分为两组,分别在餐前或餐后30min服用布南色林片2片(8mg)。受试者于服药前(0 min)和给药后0.25、0.5、0.75、1、1.5、2、3、4、6、8、12、24、36、48、60h采集静脉血。清洗1周后两组交叉用药。用LC-MS/MS法测定血浆中布南色林的浓度,并用DAS2.1.1.1程序计算药动学参数。结果 20名健康受试者空腹单次口服布南色林8mg后的主要药动学参数:ρ_(max)为(1092.08±815.34)ng·L^(-1),t_(max)为(1.06±0.39)h,t_(1/2)为(12.92±5.36)h,AUC_(0→60h)为(7341.48±4674.20)ng·h·L^(-1),AUC_(0→∞)为(7660.28±4 756.63)ng·h·L^(-1)。20名健康受试者餐后单次口服布南色林8mg后的主要药动学参数:ρ_(max)(1540.11±841.70)ng·L^(-1),t_(max)为(2.50±1.29)h,t_(1/2)为(15.12±6.39)h,AUC_(0→60h)为(12317.37±7558.19)ng·h·L^(-1),AUC_(0→∞)为(12878.34±7704.28)ng·h·L^(-1)。20名受试者给药后均无严重不良反应发生,其中7名受试者出现嗜睡,1名受试者发生一过性的尿白细胞增高,2名受试者发生一过性的肝功能异常,1周内均自行缓解。结论布南色林片空腹服用后吸收迅速,餐后服药吸收时间延迟,达峰时间显著推后,达峰浓度显著增大,进食增加药物吸收,AUC显著增大,为增加药物吸收和减少不良反应建议餐后给药。

AIM To investigate the phammcokinetic characteristics of blonanserin in Chinese healthy vonlunteers between the fasting state and the fed state respectively. METHODS According to a randomized two-period crossover de- sign, 20 healthy male volunteers were randomly divided into 2 groups with 10 in each group. The volunteers in 2 groups were administered with single dose of blonanserin tablets 8 mg in fasting state and in fed state respectively in two periods with one week washing out period. Blood samples （4 mL） were collected before （0 h） and after the administration：0.25, 0.5,0.75,1,1.5,2,3,4,6,8,12,24,36,48 and 60 h. Plasma was collected after centrifugation and plasma concentra- tions were assayed by LC-MS/MS method. The main pharmacokinetic parameters were calculated with DAS 2.1.1 soft- ware. RESULTS The main pharmacokinetic parameters of blonanserin of volunteers administered in fasting state with a single dose of 8 nag were as follows： ρmax（1 092.08 ± 815.34） ng.L-1,tmax（1.06 ± 0.39） h, t1/2（12.92 ± 5.36） h, AUC0→60h （7 341.48 ± 4 674.20） ng.h. L- 1 and AUC0→∞ （7 660.28 ± 4 756.63） ng. h. L- 1. The main phamracokinet-ie parameters of blonanserin of volunteers administered in fed state with a single dose of 8 mg were as follows： ρmax=（1 540.11 ± 841.70） ng. L-1, tmax（2.50 ± 1.29） h, t1/2（ 15.12± 6.39） h, AUC0→60h （12 317.37 ± 7 558.19） ng.h.L-1 and AUC0→∞ （12 878.34 ±7 704.28） ng.h.L-1. No severe adverse drug reactions were reported in all vol- unteers, and 7 eases of drowsiness, one case of transient urine granulocyte level escalation and one ease of transient liver dysfunction were reported. All adverse drug reactions were spontaneous remission within one week. CONCLUSION The absorption of blonanserin in the fed group prolongs significantly compared to the fasting group, while/ρmax, AUC0→60h and AUC0→∞ of the fed group increase significantly compared to the fasting group. The results coincide with the existing re- ports and it is suggested blonanserin should be taken after a meal for improving absorption and safety.