盐酸帕洛诺司琼胶囊的人体药动学及绝对生物利用度  

Pharmacokinetics and bioavailability of palonosetron hydrochloride capsules in healthy volunteers

作　　者：史香龄[1] 邵方娴[1] 宋敏[1] 杭太俊[1] 杨林[2] 文爱东[2] 张喜全[3] 戴峻[3] 王艳霞[3] 李琨[3] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]第四军医大学西京医院,西安710032 [3]江苏正大天晴药业股份有限公司研究院,南京210042

出　　处：《中国新药杂志》2013年第6期681-685,共5页Chinese Journal of New Drugs

摘　　要：目的:研究盐酸帕洛诺司琼胶囊在健康受试者体内的药动学及绝对生物利用度。方法:24例健康受试者(男12,女12),平均分为2组,按自身双交叉试验设计。一组分别单剂量口服低、高(0.25,0.75 mg)剂量;另一组分别单剂量口服和静脉注射中剂量(0.5 mg)。给药后0～168 h间隔取血。采用液相色谱-串联质谱法(LC-MS/MS)测定血浆帕洛诺司琼浓度,应用DAS 2.1程序计算药动学参数并评价口服制剂的绝对生物利用度。结果:单剂量口服0.25和0.75 mg盐酸帕洛诺司琼胶囊后的主要药动学参数Cmax分别为(0.58±0.20)和(1.95±0.94)ng.mL-1,Tmax分别为(8.4±3.9)和(8.3±2.9)h,AUC0～168分别为(35±10)和(82±34)h.ng.mL-1,t1/2分别为(74±18)和(41±9)h;单剂量0.5 mg口服与静脉注射后的主要药动学参数Cmax分别为(0.82±0.17)和(5.58±2.66)ng.mL-1,Tmax分别为(6.3±4.3)和(0.022±0.019)h,AUC0～168分别为(43±12)和(40±12)h.ng.mL-1,t1/2分别为(44±9)和(54±18)h。由AUC0～168估算,口服胶囊的绝对生物利用度为(109.9±26.1)%。结论:在0.25～0.75 mg剂量范围内口服盐酸帕洛诺司琼胶囊具有线性药动学特征;口服生物利用度较高,但是与静脉注射相比,口服给药的Cmax明显降低,Tmax显著延迟;主要药动学参数性别间无差异。Objective：To characterize the pharmacokinetics and bioavailability of palonosetron hydrochlo- ride capsules in healthy Chinese volunteers. Methods：In this randomized, crossover and self-control study, twelve healthy volunteers with equal gender were administered with single oral dose of 0. 25 or 0.75 mg palonosetron ;an- other group of twelve healthy volunteers were administered with single oral dose or intravenous injection of 0.5 mg palonosetron. Blood samples were collected in predetermined time intervals up to 168 h. The plasma concentration of palonosetron was determined by a validated LC-MS/MS method. The pharmacokinetic parameters were estimated by DAS2.1 software. Results ：The pharmacokinetic parameters of palonosetron after a single oral dose of 0.25 and 0.75 mg were as follows：Cmax（0.58±0.20） and （1.95±0.94） ng·mL-1, Tmax（8.4±3.9） and （8.3±2.9） h, AUC0-168（35± 10） and （82±34） h·ng·mL^-1,and t1/2（74±18） and （41±9） h, respectively. The Cmax after a single oral and intravenous dose of 0.5 mg were （0.82±0.17） and （5.58±2.66） ng＇mL-1 ,Tmax（6.3 4.3） and （0.022±0.019） h,AUC0-168（43±12） and （40±12） h·ng·mL^-1,t1/2（44±9） and （54±18） h,respeetively. The absolute bioavailability of palonosetron hydrochloride capsules was estimated to be （ 109.9±26. 1 ） %. Conclusion ： Linear pharmacokinetics was found for palonosetron after single oral dose in the range of 0.25 and 0.75 mg in healthy Chinese volunteers. After oral administration, the Tmax was delayed and the Cmax values were much lower compared with the intravenous injection. No significant differences were found for the pharmaeokinetie parameters between male and female volunteers （P 〉 0.05）.

关 键 词：盐酸帕洛诺司琼 药动学 绝对生物利用度 液相色谱-串联质谱法 

分 类 号：R969[医药卫生—药理学]