Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Clin Ther. 2009 Dec;31(12):3000-8. doi: 10.1016/j.clinthera.2009.12.004.
Bicalutamide is an oral nonsteroidal antiandrogen drug used during hormone ablation therapy for prostate cancer. A new generic formulation of bicalutamide has been developed.
This study was conducted to meet Korean and US regulatory requirements for the marketing of the generic 50-mg tablet formulation of bicalutamide. To this end, the pharmacokinetic properties of the new (test) formulation were compared with those of the currently marketed (reference) formulation. Tolerability was also evaluated.
An open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy Korean male volunteers. Subjects received either the test or reference formulation of bicalutamide 50-mg tablets in the first period and crossed over to the alternative formulation in the second period. Serial blood samples for pharmacokinetic analysis were taken over 672 hours after dosing. Plasma concentrations of bicalutamide were measured by HPLC-MS/MS. Pharmacokinetic parameters, including AUC(0-672h), were determined by noncompartmental analysis. Log-transformed C(max) and AUC(0-672h) for the 2 formulations were compared. Tolerability was monitored based on laboratory tests, ECGs, vital signs, and physical examinations.
Of the 34 subjects initially enrolled, 33 completed the study. The mean (SD) age, height, and weight of participants were 25.8 (4.1) years, 173.6 (5.7) cm, and 68.9 (7.8) kg, respectively. The median T(max) was 36.0 hours for both formulations. The mean (SD) t(1/2), C(max), and AUC(0-672h) for the reference formulation were 135.4 (28.6) hours, 933.2 (169.2) microg/L, and 215,680.1 (48,753.4) microg x h/L, respectively. Corresponding values for the test formulation were 134.3 (30.7) hours, 946.7 (179.9) microg/L, and 221,708.8 (54,935.1) microg x h/L. The 90% CIs for the mean ratios (test/reference) of log-transformed C(max) and AUC(0-672h) were 0.97 to 1.06 and 0.98 to 1.07, respectively. Twelve adverse events were reported for each formulation, none of which were considered drug related in the test-formulation group and 4 of which were considered drug related in the reference-formulation group (3 cases of headache, 1 case of erythematous rash).
In this single-dose study in healthy Korean male subjects, the new formulation of bicalutamide 50-mg tablets met Korean and US regulatory criteria for assumption of bioequivalence with the currently marketed formulation. Both formulations were generally well tolerated, with no clinically relevant safety concerns.
比卡鲁胺是一种用于前列腺癌激素消融治疗的口服非甾体类抗雄激素药物。现已开发出一种新的比卡鲁胺通用配方。
本研究旨在满足韩国和美国对比卡鲁胺 50mg 片剂通用配方上市的监管要求。为此，比较了新（试验）配方与当前市售（参比）配方的药代动力学特性。还评估了耐受性。
一项开放标签、随机序列、单剂量、2 期交叉研究在健康的韩国男性志愿者中进行。受试者在第一期接受比卡鲁胺 50mg 片剂的试验或参比制剂，第二期交叉至另一种制剂。给药后 672 小时内采集用于药代动力学分析的连续血样。使用 HPLC-MS/MS 测量比卡鲁胺的血浆浓度。通过非房室分析确定药代动力学参数，包括 AUC（0-672h）。比较两种制剂的对数转换 Cmax 和 AUC（0-672h）。根据实验室检查、心电图、生命体征和体格检查监测耐受性。
最初入组的 34 名受试者中，有 33 名完成了研究。参与者的平均（SD）年龄、身高和体重分别为 25.8（4.1）岁、173.6（5.7）cm 和 68.9（7.8）kg。两种制剂的中位 Tmax 均为 36.0 小时。参比制剂的平均（SD）t1/2、Cmax 和 AUC（0-672h）分别为 135.4（28.6）小时、933.2（169.2）μg/L 和 215680.1（48753.4）μg·h/L。试验制剂的相应值分别为 134.3（30.7）小时、946.7（179.9）μg/L 和 221708.8（54935.1）μg·h/L。对数转换 Cmax 和 AUC（0-672h）的平均比值（试验/参比）的 90%置信区间分别为 0.97 至 1.06 和 0.98 至 1.07。每种制剂报告了 12 起不良事件，其中没有一起在试验制剂组被认为与药物相关，而在参比制剂组有 4 起被认为与药物相关（3 例头痛，1 例红斑疹）。
在这项健康韩国男性受试者的单剂量研究中，新的比卡鲁胺 50mg 片剂配方符合韩国和美国关于与当前市售配方假设生物等效性的监管标准。两种配方通常都具有良好的耐受性，没有临床相关的安全性问题。
