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目的:研究注射用盐酸罗沙替丁醋酸酯在健康人体单、多次剂量的药动学。方法:32名健康志愿者,随机平均分为4组(男女各半),单次给药分别恒速滴注75,150,225mg,多次给药75mg,q12h×6d。按试验方案采血,高效液相色谱-质谱联用法测定血浆中罗沙替丁浓度,DAS2.0软件计算药动学参数。结果:健康受试者单次给药75,150,225mg主要药动学参数分别为:tmax(0.58±0.28),(0.63±0.23),(0.50±0.00)h;Cmax(512.3±187.6),(924.2±208.0),(1515.9±221.6)μg.L-1;t1/2β(4.2±2.0),(4.6±1.3),(4.4±0.8)h;AUC0-36h(1883.5±332.9),(3530.9±779.9),(4947.4±858.7)μg·L-1.h。多剂量给药75mg达稳态时,主要药动学参数为tmax(0.44±0.12)h;Cmax(744.9±107.4)μg·L-1;t1/2β(4.6±2.1)h;AUC0-36h(2274.2±557.0)μg.h.L-1;Cmin(21.9±5.7)μg·L-1;AUCSS(2079.5±444.3)μg·L-1.h;Cav(173.3±37.0)μg·L-1;DF(4.3±0.7)。结论:盐酸罗沙替丁醋酸酯连续多次给药后,体内无蓄积现象,血药浓度第5天已达稳态。盐酸罗沙替丁醋酸酯剂量的增加与Cmax、AUC0-36h的增加呈正相关;男女性别间差异无显著性。
Objective: To study the pharmacokinetics of rosastidine hydrochloride acetate injection in healthy single and multiple doses. Methods: Thirty-two healthy volunteers were randomly divided into 4 groups (male and female in half). Each group received 75,150,225 mg of constant-speed infusion and 75 mg twice-daily, q12h × 6 days. Blood samples were collected according to the experimental protocol, and plasma concentrations of roxatidine were determined by high performance liquid chromatography-mass spectrometry. DAS2.0 software was used to calculate pharmacokinetic parameters. Results: The main pharmacokinetic parameters of 75,150,225 mg for single administration of healthy subjects were: tmax (0.58 ± 0.28), (0.63 ± 0.23), (0.50 ± 0.00) h, Cmax (512.3 ± 187.6), (924.2 ± 208.0), (1515.9 ± 221.6) μg.L-1; t1 / 2β (4.2 ± 2.0), (4.6 ± 1.3), (4.4 ± 0.8) h; AUC0-36h (1883.5 ± 332.9), (3530.9 ± 779.9) , (4947.4 ± 858.7) μg · L-1.h. The main pharmacokinetic parameters were as follows: tmax (0.44 ± 0.12) h, Cmax (744.9 ± 107.4) μg · L-1, t1 / 2β (4.6 ± 2.1) h and AUC0-36h 2274.2 ± 557.0) μg.hL-1; Cmin (21.9 ± 5.7) μg · L-1; AUCSS (2079.5 ± 444.3) μg · L-1.h; Cav 4.3 ± 0.7). CONCLUSION: Roxatidine hydrochloride acetate has no accumulation after continuous administration for many times. The blood concentration reached the steady state on the 5th day. Roxatidine hydrochloride acetate dose increased with the Cmax, AUC0-36h increase was positively correlated; male and female gender differences was not significant.