Zaid Abdel Naser, Al Ramahi Rowa, Cortesi Rita, Mousa Ayman, Jaradat Nidal, Ghazal Nadia, Bustami Rana
Department of Pharmacy, Faculty of Medicine & health Sciences, An-Najah National University, 44859 Nablus, P.O. Box 7, Palestine.
Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy.
Sci Pharm. 2016 Jun 30;84(3):536-546. doi: 10.3390/scipharm84030536.
There is a wide inter-individual response to statin therapy including rosuvastatin calcium (RC), and it has been hypothesized that genetic differences may contribute to these variations. In fact, several studies have shown that pharmacokinetic (PK) parameters for RC are affected by race. The aim of this study is to demonstrate the interchangeability between two generic RC 20 mg film-coated tablets under fasting conditions among Mediterranean Arabs and to compare the pharmacokinetic results with Asian and Caucasian subjects from other studies. A single oral RC 20 mg dose, randomized, open-label, two-way crossover design study was conducted in 30 healthy Mediterranean Arab volunteers. Blood samples were collected prior to dosing and over a 72-h period. Concentrations in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method. Twenty-six volunteers completed the study. Statistical comparison of the main PK parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric mean %) were 107.73 (96.57-120.17), 103.61 (94.03-114.16), and 104.23 (94.84-114.54) for peak plasma concentration (C), Area Under the Curve (AUC), and AUC, respectively. The 90% confidence intervals were within the pre-defined limits of 80%-125% as specified by the Food and Drug Administration and European Medicines Agency for bioequivalence studies. Both formulations were well-tolerated and no serious adverse events were reported. The PK results (AUC and C) were close to those of the Caucasian subjects. This study showed that the test and reference products met the regulatory criteria for bioequivalence following a 20 mg oral dose of RC under fasting conditions. Both formulations also showed comparable safety results. The PK results of the test and reference in the study subjects fall within the acceptable interval of 80%-125% and they were very close to the results among Caucasians. These PK results may be useful in order to determine the suitable RC dose among Arab Mediterranean patients.
包括瑞舒伐他汀钙（RC）在内，个体对他汀类药物治疗的反应存在很大差异，据推测，基因差异可能是导致这些差异的原因。事实上，多项研究表明，RC的药代动力学（PK）参数受种族影响。本研究的目的是证明两种通用的20 mg薄膜包衣RC片剂在地中海阿拉伯人空腹条件下的可互换性，并将药代动力学结果与其他研究中的亚洲和白种人受试者进行比较。在30名健康的地中海阿拉伯志愿者中进行了一项单剂量口服20 mg RC的随机、开放标签、双向交叉设计研究。在给药前和72小时内采集血样。使用经过验证的液相色谱串联质谱法对血浆浓度进行定量。26名志愿者完成了研究。主要PK参数的统计比较显示，通用产品和品牌产品之间无显著差异。血浆峰浓度（C）、曲线下面积（AUC）和AUC的点估计值（几何平均百分比比值）分别为107.73（96.57 - 120.17）、103.61（94.03 - 114.16）和104.23（94.84 - 114.54）。90%置信区间在食品药品监督管理局和欧洲药品管理局规定的生物等效性研究预定义的80% - 125%范围内。两种制剂耐受性良好，未报告严重不良事件。PK结果（AUC和C）与白种人受试者相近。本研究表明，空腹条件下口服20 mg RC后，受试产品和参比产品符合生物等效性的监管标准。两种制剂的安全性结果也具有可比性。研究对象中受试产品和参比产品的PK结果落在80% - 125%的可接受区间内，且与白种人的结果非常接近。这些PK结果可能有助于确定阿拉伯地中海患者合适的RC剂量。
