Xu H R, Chen W L, Chu N N, Li X N, Zhu J R
Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
J Biomed Biotechnol. 2012;2012:386230. doi: 10.1155/2012/386230. Epub 2012 Jul 1.
The aim of this study was to evaluate the difference in pharmacokinetics and pharmacodynamics between extended-release (ER) fluvastatin tablet and its immediate-release (IR) capsule in Chinese healthy subjects. This was an open-label, single/multiple-dose, two-period, two-treatment, crossover, randomized trial with a minimum washout period of 7 days. Twenty healthy male adult subjects were given fluvastatin ER tablet 80 mg QD by oral administration or fluvastatin IR capsule 40 mg BID for seven days. Blood samples were collected up to 24 hours after dosing on day 1 and day 7. Serum concentrations of fluvastatin were determined by LC-MS/MS. For fluvastatin ER tablet 80 mg QD, C(max) was 61.0 ± 39.0 and 63.9 ± 29.7 ng/mL, and AUC(0-24 h) was 242 ± 156 and 253 ± 91.1 ng·h/mL on day 1 and 7, respectively. For fluvastatin IR capsule 40 mg BID, C(max) was 283 ± 271 and 382 ± 255 ng/mL, and AUC(0-24 h) was 720 ± 776 and 917 ± 994 ng·h/mL on day 1 and day 7, respectively. The relative bioavailability of fluvastatin ER tablet 80 mg QD to fluvastatin IR capsule 40 mg BID is (45.3 ± 23.9)% and (43.3 ± 24.1)% on day 1 and day 7, respectively. T(max) for fluvastatin ER tablet was 2.50 and 2.60 h and for capsule was 0.78 and 0.88 h on day 1 and day 7, respectively. In the first period, compared to baseline, cholesterol decreased 15.3% in fluvastatin ER tablet 80 mg QD and 16.9% in fluvastatin IR capsule 40 mg BID. Triglyceride decreased 3.7% in fluvastatin ER tablet 80 mg QD and 19.1% in fluvastatin IR capsule 40 mg BID. The difference has no statistical significance at P > 0.05 in reduction percent of cholesterol and triglyceride between the two groups. No adverse events were recorded. The results indicated that C(max) of fluvastatin ER tablet is reduced and T(max) is prolonged compared with IR capsule. There is no accumulation for ER formulation after multiple doses.
本研究旨在评估在中国健康受试者中，缓释氟伐他汀片与其速释胶囊在药代动力学和药效学方面的差异。这是一项开放标签、单剂量/多剂量、两周期、两治疗、交叉、随机试验，最短洗脱期为7天。20名健康成年男性受试者口服给予氟伐他汀缓释片80mg每日一次或氟伐他汀速释胶囊40mg每日两次，持续7天。在第1天和第7天给药后24小时内采集血样。采用液相色谱-串联质谱法测定氟伐他汀的血清浓度。对于氟伐他汀缓释片80mg每日一次，第1天和第7天的C(max)分别为61.0±39.0和63.9±29.7ng/mL，AUC(0-24h)分别为242±156和253±91.1ng·h/mL。对于氟伐他汀速释胶囊40mg每日两次，第1天和第7天的C(max)分别为283±271和382±255ng/mL，AUC(0-24h)分别为720±776和917±994ng·h/mL。氟伐他汀缓释片80mg每日一次相对于氟伐他汀速释胶囊40mg每日两次的相对生物利用度在第1天和第7天分别为(45.3±23.9)%和(43.3±24.1)%。氟伐他汀缓释片的T(max)在第1天和第7天分别为2.50和2.60小时，胶囊的T(max)在第1天和第7天分别为0.78和0.88小时。在第一周期，与基线相比，氟伐他汀缓释片80mg每日一次组胆固醇降低15.3%，氟伐他汀速释胶囊40mg每日两次组胆固醇降低16.9%。氟伐他汀缓释片80mg每日一次组甘油三酯降低3.7%，氟伐他汀速释胶囊40mg每日两次组甘油三酯降低19.1%。两组胆固醇和甘油三酯降低百分比的差异在P>0.05时无统计学意义。未记录到不良事件。结果表明，与速释胶囊相比，氟伐他汀缓释片的C(max)降低，T(max)延长。多次给药后缓释制剂无蓄积。
