Kim Kyoung-Ah, Park Ji-Young
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, 126-1, 5-Ga, Anam-dong, Sungbuk-Gu, Seoul, 136-705, Korea.
Clin Drug Investig. 2013 Dec;33(12):913-9. doi: 10.1007/s40261-013-0140-7.
Bepotastine is a second-generation histamine H(1) receptor antagonist that is indicated in allergic rhinitis, urticaria, and pruritus associated with skin disease. The aim of the present study was to compare the pharmacokinetics of two different bepotastine formulations [bepotastine besilate 10 mg (reference) and bepotastine salicylate 9.64 mg (test)], both containing 7.11 mg bepotastine base, to satisfy regulatory requirements for marketing.
A single-center, randomized, single-dose, open-label, two-period, two-sequence crossover study with a 7-day washout period was conducted in 26 healthy male subjects. Plasma samples for drug analysis were collected up to 24 h after drug treatment. Pharmacokinetic parameters, including maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), were calculated. ANOVA for bioequivalence was conducted using log-transformed C(max) and AUC values, and the mean ratios and their 90 % confidence intervals were calculated.
Of the 26 participants initially enrolled, 24 healthy participants completed both treatment periods. All pharmacokinetic parameters of bepotastine exhibited no significant differences between the two formulations. The observed mean (standard deviation) C(max), AUC from time zero to the time of the last measurable concentration (AUC(last)), and AUC from time zero to infinity (AUC(∞)) values for the reference formulation were 99.9 (31.4) ng/mL, 388.9 (102.6) ng·h/mL, and 392.4 (103.6) ng·h/mL, respectively. Corresponding values for the test formulation were 101.0 (26.3) ng/mL, 389.8 (112.2) ng·h/mL, and 393.7 (111.7) ng·h/mL. The geometric mean ratios (90 % CI) between the two formulations were 1.0220 (0.9224-1.1324) for C(max), 0.9928 (0.9521-1.0351) for AUC(last), and 0.9959 (0.9549-1.0387) for AUC(∞). During the study period, two adverse events were reported in the test formulation group, but both were transient, mild, and resolved completely during the treatment period. These adverse events were considered unrelated to the study drugs.
The results of the present study revealed that bepotastine besilate 10 mg (reference) and bepotastine salicylate 9.64 mg (test) formulations have comparable pharmacokinetic characteristics and that these two formulations meet the regulatory criteria for bioequivalence. Both bepotastine formulations were generally well-tolerated in this population.
贝波司汀是一种第二代组胺H(1)受体拮抗剂，适用于过敏性鼻炎、荨麻疹以及与皮肤病相关的瘙痒症。本研究的目的是比较两种不同贝波司汀制剂[10 mg苄磺酸盐贝波司汀（参比制剂）和9.64 mg水杨酸盐贝波司汀（受试制剂），二者均含7.11 mg贝波司汀碱]的药代动力学，以满足上市的监管要求。
在26名健康男性受试者中开展了一项单中心、随机、单剂量、开放标签、两周期、两序列交叉研究，洗脱期为7天。在药物治疗后24小时内采集用于药物分析的血浆样本。计算药代动力学参数，包括最大血浆浓度（C(max)）和血浆浓度-时间曲线下面积（AUC）。使用对数转换后的C(max)和AUC值进行生物等效性的方差分析，并计算平均比值及其90%置信区间。
最初纳入的26名参与者中，24名健康参与者完成了两个治疗周期。贝波司汀的所有药代动力学参数在两种制剂之间均无显著差异。参比制剂观察到的平均（标准差）C(max)、从零时间到最后可测浓度时间的AUC（AUC(last)）以及从零时间到无穷大的AUC（AUC(∞)）值分别为99.9（31.4）ng/mL、388.9（102.6）ng·h/mL和392.4（103.6）ng·h/mL。受试制剂的相应值分别为101.0（26.3）ng/mL、389.8（112.2）ng·h/mL和393.7（111.7）ng·h/mL。两种制剂之间的几何平均比值（90%CI）对于C(max)为1.0220（0.9224 - 1.1324），对于AUC(last)为0.9928（0.9521 - 1.0351），对于AUC(∞)为0.9959（0.9549 - 1.0387）。在研究期间，受试制剂组报告了两例不良事件，但均为短暂性、轻度，且在治疗期间完全缓解。这些不良事件被认为与研究药物无关。
本研究结果表明，10 mg苄磺酸盐贝波司汀（参比制剂）和9.64 mg水杨酸盐贝波司汀（受试制剂）具有可比的药代动力学特征，且这两种制剂符合生物等效性的监管标准。两种贝波司汀制剂在该人群中总体耐受性良好。
