Trabelsi Fethi, Bartůnek Aleš, Vlavonou Raphaël, Navrátilová Lucie, Dubé Charlotte, Tanguay Mario, Hauser Tomáš
PharmaNet Canada Inc, Montreal, Quebec, Canada.
Int J Clin Pharmacol Ther. 2012 Oct;50(10):741-50. doi: 10.5414/CP201687.
Rosuvastatin, a synthetic lipid-lowering agent acts selectively by competitive inhibition of 3-hydroxy- 3-methylglutaryl-coenzyme A. It is indicated as an adjunct to diet in patients with hypercholesterolemia and mixed dyslipidemia.
The purpose of this study was to demonstrate bioequivalence between a generic rosuvastatin 40 mg tablet (Zentiva, Prague, Czech Republic) and a reference product (Crestor, AstraZeneca, Luton, UK), under fasting conditions as required by the European Medicinal Agency.
A single-oral 40 mg-dose, randomized, open-label, 2-way crossover design study was conducted in 42 healthy volunteers under fasting conditions. Rosuvastatin was administered following an overnight-fast in two occasions with a 14-day washout period in-between. Blood samples were collected in EDTA-K2 tubes prior to dosing and over a 96-hour period. Rosuvastatin was measured in plasma using an automated LC-MS/MS assay (range 81.02 - 40,512.00 pg/ml). Pharmacokinetics were performed using non-compartmental analyses approach to evaluate AUC(last), AUC∞ and C(max). ANOVA was performed on the ln-transformed data and the 90% Confidence Interval (CI) was determined. Bioequivalence will be concluded if the 90% CI falls within 80.00 - 125.00% for AUC(last) and C(max). Safety and tolerability were also evaluated.
39 volunteers completed the study and were considered for the pharmacokinetic and statistical analyses. Descriptive safety data analyses were performed on all subjects. All pharmacokinetic parameters met the acceptance criteria as the 90% CI were within 80.00 - 125.00%. Both formulations were well tolerated and no serious adverse events were reported.
This study showed that the test and reference products met the regulatory criteria for bioequivalence following a 40 mg oral dose under fasting conditions.
瑞舒伐他汀是一种合成降脂药物，通过竞争性抑制3-羟基-3-甲基戊二酰辅酶A发挥选择性作用。它被用作高胆固醇血症和混合性血脂异常患者饮食治疗的辅助药物。
本研究旨在按照欧洲药品管理局的要求，在空腹条件下证明仿制的40毫克瑞舒伐他汀片剂（捷克共和国布拉格的 Zentiva公司生产）与参比产品（英国卢顿的阿斯利康公司生产的可定）之间的生物等效性。
在42名健康志愿者中进行了一项单剂量口服40毫克、随机、开放标签、双向交叉设计的研究，研究在空腹条件下进行。瑞舒伐他汀在禁食过夜后分两次给药，两次给药之间有14天的洗脱期。在给药前及96小时内，采集乙二胺四乙酸二钾（EDTA-K2）抗凝管中的血样。使用自动液相色谱-串联质谱法（检测范围81.02 - 40512.00皮克/毫升）测定血浆中的瑞舒伐他汀。采用非房室分析方法进行药代动力学研究，以评估曲线下面积（AUC(last)）、AUC∞和峰浓度（C(max)）。对经自然对数转换的数据进行方差分析，并确定90%置信区间（CI）。如果AUC(last)和C(max)的90%CI落在80.00 - 125.00%范围内，则可得出生物等效性的结论。同时还评估了安全性和耐受性。
39名志愿者完成了研究，并纳入药代动力学和统计学分析。对所有受试者进行了描述性安全性数据分析。所有药代动力学参数均符合接受标准，因为90%CI在80.00 - 125.00%范围内。两种制剂耐受性良好，未报告严重不良事件。
本研究表明，在空腹条件下口服40毫克剂量后，受试产品和参比产品符合生物等效性的监管标准。
