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目的评价盐酸安妥沙星片在中国健康受试者空腹和餐后多剂给药的药代动力学。方法按随机、开放、多剂量(200,400,600 mg)空腹和餐后多次口服给药的方法进行设计。每个剂量组各有8名受试者(男4例、女4例)在空腹和餐后条件下连续7 d口服规定剂量的盐酸安妥沙星片。第1天和第7天给药后收集不同时间点的血、尿样本,用HPLC法测定浓度。结果3个剂量组空腹和餐后连续7 d口服盐酸安妥沙星片200,400,600 mg的主要药代动力学参数如下:第1天空腹口服的C_(max)分别为(2.23±0.38),(4.59±1.40),(5.03±0.77)mg·L~(-1),t_(1/2β)分别为(11.99±3.31),(10.97±5.33),(14.39±1.63)h,t_(max)分别为(1.37±0.78),(2.04±1.42),(2.90±2.02)h,AUC_(0-t)分别为(27.61±6.14),(51.77±22.09),(73.62±10.14)mg·L~(-1)·h,AUC0-∞分别为(38.28±13.49),(72.28±42.80),(108.91±13.26)mg·L~(-1)·h,V/F(92.84±12.98),(91.90±14.55),(116.28±22.62)L,CL/F(5.73±1.71),(7.67±4.65),(5.58±0.66)L·h~(-1);第1天餐后口服的C_(max)分别为(2.36±0.43),(4.11±1.53),(5.60±1.00)mg·L~(-1),t_(1/2β)分别为(14.37±4.34),(11.25±5.39),(15.53±2.94)h,t_(max)分别为(2.69±1.62),(2.40±1.50),(2.65±1.29)h,AUC_(0-t)分别为(33.69±4.00),(48.07±22.19),(78.01±17.18)mg·L~(-1)·h,AUC0-∞分别为(50.71±8.86),(67.37±41.98),(121.31.66±33.54)mg·L~(-1)·h,V/F分别为(81.04±16.35),(106.32±34.33),(114.08±20.00)L,CL/F分别为(4.07±0.82),(8.28±5.29),(5.23±1.18)L·h~(-1);第7天稳态后空腹口服的C_(max)分别为(3.69±1.39),(7.54±2.95),(8.50±0.93)mg·L~(-1),t_(1/2β)分别为(25.22±3.34),(19.56±12.47),(15.95±2.85)h,t_(max)分别为(1.64±1.29),(1.31±0.79),(1.60±1.07)h,AUC_(0-t)分别为(72.29±24.00),(142.96±67.20),(180.81±35.33)mg·L~(-1)·h,AUC0-∞分别为(75.90±25.46),(148.26±69.86),(183.30±35.11)mg·L~(-1)·h,V/F分别为(184.77±52.51),(119.22±53.92),(118.91±30.13)L,CL/F分别为(5.06±1.18),(4.75±1.72),(5.15±0.72)L·h~(-1);第7天稳态后餐后口服的C_(max)分别为(3.53±1.06),(6.54±1.43),(8.52±1.80)mg·L~(-1),t_(1/2β)分别为(24.08±6.12),(20.64±9.16),(18.69±6.49)h,t_(max)分别为(2.94±1.02),(1.96±1.05),(2.69±0.96)h,AUC_(0-t)分别为(94.71±31.03),(142.17±52.46),(211.34.01±52.99)mg·L~(-1)·h,AUC0-∞分别为(99.32±33.93),(149.77±55.19),(213.76±53.00)mg·L~(-1)·h,V/F分别为(139.40±37.39),(140.24±71.11),(130.20±71.09)L,CL/F分别为(4.11±1.13),(4.81±1.17),(4.69±0.88)L·h~(-1)。多剂量口服盐酸安妥沙星200,400,600 mg第7天给药后,0~120 h原型药物尿中累积排泄百分率分别为(67.24±13.56)%,(68.62±14.45)%,(74.31.±12.99)%。结论空腹和餐后多剂口盐酸安妥沙星片服200,400,600 mg,t_(max)延长,体内无蓄积,进食对药代参数影响不明显,临床应用可不考虑饮食的影响。
Objective To evaluate the pharmacokinetics of amphetamine tablets in fasting and postprandial multi-dose Chinese healthy subjects. Methods Randomized, open, multi-dose (200,400,600 mg) fasting and postprandial oral administration of multiple methods of design. Each dose group, each of eight subjects (4 males and 4 females) was given a prescribed dose of amphotoxin hydrochloride tablets under fasting and postprandial conditions for 7 consecutive days. Blood and urine samples were collected at different time points after administration on days 1 and 7, and the concentrations were determined by HPLC. Results The main pharmacokinetic parameters of 200,400,600 mg of anoxetine hydrochloride tablets administered fasting and postprandially for 7 consecutive days were as follows: The maximal oral C max values were (2.23 ± 0.38) and (4.59 ± 1.40, 5.03 ± 0.77 mg · L -1 and 1 / 2β were (11.99 ± 3.31), (10.97 ± 5.33), (14.39 ± 1.63) h and t max respectively were (27.61 ± 6.14), (51.77 ± 22.09) and (73.62 ± 10.14) mg · L ~ (-1) respectively in the control group (1.37 ± 0.78, 2.04 ± 1.42 and 2.90 ± 2.02 h, 1) · h and AUC0-∞ were respectively (38.28 ± 13.49), (72.28 ± 42.80), (108.91 ± 13.26) mg · L -1 · h, V / F 92.84 ± 12.98 and 91.90 ± (Max) was 14.55 (116.28 ± 22.62) L, CL / F (5.73 ± 1.71), (7.67 ± 4.65) and (5.58 ± 0.66) L · h (2.36 ± 0.43), (4.11 ± 1.53) and (5.60 ± 1.00) mg · L -1 respectively, and the values of t 1 / 2β were (14.37 ± 4.34), (11.25 ± 5.39) and ± 2.94) h and t max were (2.69 ± 1.62), (2.40 ± 1.50) and (2.65 ± 1.29) h, respectively. The AUC_ (0-t) were 33.69 ± 4.00 and 48.07 ± 22.19, (78.01 ± 17.18) mg · L -1 · h and AUC 0 -∞ were (50.71 ± 8.86), (67.37 ± 41.98) and (121.31.66 ± 33.54) mg · L -1 · h respectively , V / F were (81.04 ± 16.35), (106.32 ± 34.33), (114.08 ± 20.00) L, CL / F (4.07 ± 0.82), (8.28 ± 5.29) and (5.23 ± 1.18) L · h ~ (-1) respectively. On day 7, the fasting oral C max was (3.69 ± 1.39), ( 7.54 ± 2.95, and 8.50 ± 0.93 mg · L -1, respectively. The values of t 1 / 2β were (25.22 ± 3.34), (19.56 ± 12.47) and (15.95 ± 2.85) h, respectively, (1.64 ± 1.29), (1.31 ± 0.79), (1.60 ± 1.07) h, respectively. The AUC_ (0-t) were (72.29 ± 24.00), (142.96 ± 67.20) and (180.81 ± 35.33) mg · L ~ (-1) · h and AUC0-∞ were (75.90 ± 25.46), (148.26 ± 69.86) and (183.30 ± 35.11) mg · L -1 · h, respectively. The V / F values were (184.77 ± 52.51) , (119.22 ± 53.92) and (118.91 ± 30.13) L, respectively. The CL / F were 5.06 ± 1.18, 4.75 ± 1.72 and 5.15 ± 0.72 L · h ~ The post-prandial oral C max values were (3.53 ± 1.06), (6.54 ± 1.43) and (8.52 ± 1.80) mg · L -1, respectively, with t 1/2 (24.08 ± 6.12) , (20.64 ± 9.16), (18.69 ± 6.49) h and t max respectively were (2.94 ± 1.02), (1.96 ± 1.05), (2.69 ± 0.96) h and AUC_ (0-t) were 94.71 ± AUC0-∞ were (99.32 ± 33.93), (149.77 ± 55.19) and (213.76 ± 53.00) mg / L, respectively, which were significantly higher than those of the control group (31.03), (142.17 ± 52.46) and (211.34.01 ± 52.99) mg · L -1 · L ~ (-1) · h and V / F were (139.40 ± 37.39), (140.24 ± 71.11) and (130.20 ± 71.09) L, respectively .13), (4.81 ± 1.17) and (4.69 ± 0.88) L · h ~ (-1), respectively. The cumulative excretion rates of urinary excretion of prototype drugs from 0 to 120 h after oral administration of amphetamine hydrochloride 200,400,600 mg on day 7 were (67.24 ± 13.56)%, (68.62 ± 14.45)% and (74.31 ± 12.99)% respectively, . Conclusion Fasting and postoperative multidispersed tablets of antitussive hydrochloride amphetamine tablets 200,400,600 mg, t_ (max) prolonged, no accumulation in the body, eating on the pharmacokinetic parameters had no obvious clinical application may not consider the impact of diet.