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盐酸地尔硫延迟缓释微丸胶囊的人体药动学研究 被引量:1

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers
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摘要 目的 研究盐酸地尔硫[艹卓]延迟缓释微丸胶囊在健康成年人体内的药物动力学特征。方法 采用随机、开放、平行试验设计,24名健康受试者随机分成3组,每组8名,男女各半,分别单次口服低、中、高(90、180、270mg)盐酸地尔硫[艹卓]延迟缓释微丸胶囊,低剂量组每日1次口服90mg盐酸地尔硫[艹卓]延迟缓释微丸胶囊共6d多次给药。在不同时间点取静脉血,采用反相高效液相色谱法测定地尔硫[艹卓]的血药浓度。用DASVer2.0软件进行药物动力学参数计算。结果 健康受试者单剂量口服试验制剂盐酸地尔硫[艹卓]延迟缓释微丸胶囊90、180及270mg的主要药物动力学参数(均数±标准差)tmax分别为(8.8±2.0)、(10.5±1.4)和(11.0±1.1)h,Cmax分别为(67.43±32.74)、(169.44±92.00)和(191.23±81.81)ng·ml^-1,t1/2β分别为(14.6±7.8)、(16.9±6.3)和(16.0±6.1)h,AUC0~t分别为(1018.1±524.3)、(3069.1±1727.7)和(3749.5±1557.5)ng·h·mL^-1,AUC0~∞分别为(1470.5±814.7)、(4556.2±3128.3)和(5042.9±1861.7)ng·h·mL^-1。健康受试者多剂量口服盐酸地尔硫[艹卓]延迟缓释微丸胶囊主要药物动力学参数(均数±标准差)tmax为(9.0±2.3)h,Cmax为(81.92±33.70)ng.mL^-1,t1/2β为(14.3±7.7)h,AUC0-t为(1365.9±569.5)ng·h·mL^-1,AUC0~∞为(1814.5±1021.8)ng.h.mL^-1,Cav为(46.66±16.36)ng·mL^-1,DF为(1.1±0.4)。结论 盐酸地尔硫[艹卓]延迟缓释微丸胶囊释药时间明显滞后,达峰时间明显延长,具有延迟缓释特征。 Objective To determine diltiazem in the human plasma by reversed-phase high-performance liquid chromatography (RP-HPLC), and to study the pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers. Methods Three single oral doses (90, 180 mg, and 270 mg) and a multiple oral dose (90 mg. d^-1 * 6d) were given to 24 volunteers in an open randomized parallel design. Plasma concentrations of diltiazem were determined by RP-HPLC, Its pharmacokinetic parameters were calculated by DAS Ver 2.0. Results The main pharmacokinetic parameters of diltiazem hydrochloride delayed-onest sustained-release pellet capsules after a single ora190, 180, and270 mgwereas follows: tmax was (8.8±2.0), (10.5±1.4), and (11.0±1.1) h; Cmax was (67.43±32.74), (169.44±92.00), and (191. 23±81. 81) ng.mL^-1; t1/2β was (14.6±7.8), (16.9±6.3), and (16.0±6.1) h; AUC0-t was (1 018.1±524.3), (3069.1±1 727.7), and (3749.5±1557.5) ng.h. mL^-1 ; AUC0-∞ was (1 470. 5±814.7), (4 556.2±3 128.3), and (5 042.9±1 861.7) ng . h . mL^-1. The main pharmacokinefic parameters of dihiazem hydrochloride delayed-onset sustained-release pellet capsules after a multiple oral dose were as follows. tmax was (9. 0±2. 3) h; Cmax was (81.92±33. 70) ng . mL^-1 ; t1/2β was (14. 3±7. 7) h; AUC0-t was (1 365.9±569.5) ng. h . mL^-1; AUC0-∞was (1 814. 5±1 021.8) ng . h . mL^-1 ; Cav was (46. 66± 16. 36) ng . mL^-1 ; and DF was (1.1±0. 4). Conclusion Diltiazem hydrochloride delay-onset sustained-release pellet capsules had marked characteristics of delayed and controlled release.
出处 《中南药学》 CAS 2007年第5期463-467,共5页 Central South Pharmacy
关键词 盐酸地尔硫[艹卓]延迟缓释微丸胶囊 药物动力学 反相高效液相色谱法 diltiazem hydrochloride delay-onset sustained-release pellet capsules pharmacokinetics RP-HPLC
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