注射用兰索拉唑在健康人体内单、多剂量的药动学研究

Study on pharmacokinetics of single and multi-dose lansoprazole injection in healthy volunteers

目的研究注射用兰索拉唑在中国健康人体内的单、多剂量药动学。方法24名健康志愿者随机分为3组,每组8人(男女各半),分别恒速静脉注射15、30、60 mg兰索拉唑进行单剂量药动学研究,30 mg剂量组继续给药,qd×7d,进行多剂量药动学研究。按试验方案采血,用高效液相色谱法测定血药浓度,DAS 2.0程序计算药动学参数。结果健康受试者单剂量给药15、30、60 mg兰索拉唑后主要的药动学参数分别为t_(max)(0.669±s 0.014)、(0.667±0.012)、(0.668±0.013)h;c_(max)(1.01±0.05)、(1.69±0.06)、(3.01±0.08)mg·L^(-1);AUC_(0～t)(3.8±0.3)、(6.5±0.3)、(10.26±0.24)mg·h·L^(-1);t_(1/2)(1.8±0.6)、(3.4±0.8)、(2.5±0.5)h。多剂量给药30 mg达稳态时,主要的药动学参数为t_(max)(0.668±0.011)h;c_(max)(1.74±0.05)mg·L^(-1);c_(min)(0.125±0.012)mg·L^(-1);AUC_(?)(6.5±0.3)mg·h·L^(-1);t_(1/2)(3.0±0.9)h;CL (3.8±0.4)L.h^(-1);c_(av)(0.271±0.014)mg·L^(-1);DF(6.0±0.4)%。结论兰索拉唑在连续多次给药后,体内无蓄积现象,血药浓度d4已达稳态。兰索拉唑剂量的增加与C_(max)、AUC_(0～1)和AUC_(0～∞)的增加呈正相关关系;兰索拉唑的体内过程在男女性别间无显著差异。

AIM To study the pharmacokinetics of lansoprazole injection with a single and multiple-dose intravenous injection administration using a constant speed in Chinese healthy volunteers. METHODS Twentyfour healthy volunteers were randomly divided into three groups, with 4 males and 4 females in each group. The volunteers in three groups were administrated with single dose of lansoprazole 15, 30, 60 mg, respectively, and those who got dose of 30 mg were administrated once a day till seventh day. Blood samples were collected according to the protocol and serum concentrations of lansoprazole, and in term were measured by validated high pressure liquid chromatography （HPLC） . DAS2.0 pharmacokinetic program was performed for calculating pharmacokinetic parameters. RESULTS The main pharmacokinetic parameters of lansoprazole in volunteers who were administrated with a single dose of 15, 30, 60 mg were as follows： tmax （0.669 ± s 0.014）, （0.667 ± 0.012）, （0.68 ± 0.013） h; cmax （1.01 ± 0.05）, （1.69 ± 0.06）, （3.01± 0.08） mg·L^-1; AUC0-1 （3.8 ± 0.3）, （6.5 ± 0.3）, （10.26 ± 0.24） mg·h·L^-1; t1/2 （1.8 ± 0.6）, （3.4 ± 0.8）, （2.5 ± 0.5） h; respectively. The main pharmacokinetic parameters of lansoprazole after multiple-dose （30 mg） administration were as follows： tmax （0.68 ± 0.011） h; cmax, （1.74 ± 0.05） mg·L^-1; cmax, （0.125 ± 0.012） mg·L^-1; AUCav （6.5 ± 0.3） mg·h·L^-1; t1/2 （3.0 ± 0.9） h; CL （3.8 ± 0.4） L·h^1; cav （0.271 ± 0.014） mg·L^-1; DF （6.0 ± 0.4） %. CONCLUSION After administration of multiple-dose lansoprazole, no accumulation occur in vivo. Serum concentrations of lansoprazole have been in steady state till fourth day. Increase of lansoprazole dosage is positively calculated with increase of cmax, A UC0-1 and A UC0-∞ and simultaneously with no significant difference of physiological disposition between the male and female.