Martin Paul D, Warwick Mike J, Dane Aaron L, Cantarini Mireille V
AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Clin Ther. 2003 Aug;25(8):2215-24. doi: 10.1016/s0149-2918(03)80214-x.
Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been developed for the treatment of patients with dyslipidemia.
This study assessed the dose proportionality and pharmacokinetics of single oral doses of rosuvastatin in healthy volunteers.
This was a double-blind, randomized, incomplete crossover trial consisting of 3 trial days separated by >/=7-day washout periods. Healthy men were allocated to 1 of 2 treatment regimens: rosuvastatin 10, 20, and 80 mg, or rosuvastatin 10, 40, and 80 mg, administered as single doses on separate trial days in random order. Pharmacokinetic and tolerability assessments were made up to 96 hours after administration. Dose proportionality was tested using the power-law approach.
Eighteen healthy white men participated in the trial (mean age, 41.2 years; mean height, 178.4 cm; mean body weight, 81.6 kg). Geometric mean rosuvastatin maximum plasma concentration (C(max)) values of 3.75, 6.79, 10.3, and 30.1 ng/mL were achieved at a median time to C(max) of 5.0 hours after doses of 10, 20, 40, and 80 mg, respectively. The corresponding geometric mean values for rosuvastatin area under the plasma concentration-time curve from time 0 to time of the last measurable concentration (AUC(0-t)) were 31.6, 56.8, 98.2, and 268 ng.h/mL. C(max) and AUC(0-t) were both linearly related to dose. The estimates of the proportionality coefficient (90% CI) for CmaX and AUC(o-t) were 0.999 (0.898-1.099) and 1.024 (0.941-1.107), respectively; all values fell within the prespecified range of 0.847 to 1.153. Rosuvastatin was well tolerated in this group of healthy men when administered orally at doses of 10 to 80 mg.
Rosuvastatin systemic exposure was dose proportional over the dose range of 10 to 80 mg.
瑞舒伐他汀是一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，已被开发用于治疗血脂异常患者。
本研究评估了健康志愿者单次口服瑞舒伐他汀的剂量比例关系和药代动力学。
这是一项双盲、随机、不完全交叉试验，包括3个试验日，间隔≥7天的洗脱期。健康男性被分配到2种治疗方案中的1种：瑞舒伐他汀10、20和80mg，或瑞舒伐他汀10、40和80mg，在不同的试验日以随机顺序单次给药。给药后长达96小时进行药代动力学和耐受性评估。使用幂律方法测试剂量比例关系。
18名健康白人男性参与了试验（平均年龄41.2岁；平均身高178.4cm；平均体重81.6kg）。分别给予10、20、40和80mg剂量后，瑞舒伐他汀的最大血浆浓度（C(max)）几何平均值分别为3.75、6.79、10.3和30.1ng/mL，达到C(max)的中位时间为5.0小时。从0时间到最后可测量浓度时间的血浆浓度-时间曲线下瑞舒伐他汀的相应几何平均值（AUC(0-t)）为31.6、56.8、98.2和268ng·h/mL。C(max)和AUC(0-t)均与剂量呈线性相关。CmaX和AUC(o-t)的比例系数（90%CI）估计值分别为0.999（0.898-1.099）和1.024（0.941-1.107）；所有值均落在预先设定的0.847至1.153范围内。在这组健康男性中，口服10至80mg剂量的瑞舒伐他汀耐受性良好。
在10至80mg的剂量范围内，瑞舒伐他汀的全身暴露量与剂量成比例。
