Zhu Yubing, Zhang Qian, Zou Jianjun, Wan Meng, Zhao Zheng, Zhu Junrong
Department of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Laboratory of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Drug Des Devel Ther. 2015 Aug 12;9:4621-9. doi: 10.2147/DDDT.S86415. eCollection 2015.
Ondansetron oral soluble film is designed to be applied on top of the tongue without requiring water to aid dissolution or swallowing, which is especially fitting for nausea and vomiting patients.
This study was conducted to compare the bioavailability of two 8 mg ondansetron oral soluble film formulations.
This randomized, open-label, two-period crossover study was performed under fasting conditions. A total of ten eligible subjects were randomly assigned at a 1:1 ratio to receive a single 8 mg dose of the test and reference ondansetron oral soluble film formulations, followed by a 1-week washout period and administration of the alternate formulation. The concentrations of ondansetron were assayed using an liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) method. For analysis of pharmacokinetic properties, including the peak concentration of T max (C max), AUC from time 0 (baseline) to t hours (AUC0- t ), and AUC from baseline to infinity (AUC0-∞), blood samples were obtained at intervals over the 24-hour period after studying drug administration. Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and by questioning subjects about adverse events.
The mean (standard derivation [SD]) relative bioavailability was 96.5 (23.7%). The 90% confidence intervals (CIs) for the log-transformed ratios of C max and AUC0- t were 84.71%-103.28% and 91.38%-108.60%, respectively (P>0.05). Similar results were found for the data without log-transformation. No statistically significant differences were found based on analysis of variance. No significant adverse events occurred or were reported during the study.
As the 90% CIs based on the differences between the test and reference formulation were within the 80%-125% range for both the C max and AUC0- t , we concluded that the two formulations were bioequivalent with respect to the rate or the extent of absorption. Both formulations are well tolerated.
昂丹司琼口腔可溶性薄膜设计用于置于舌上，无需用水辅助溶解或吞咽，这对恶心和呕吐患者尤为适用。
本研究旨在比较两种8毫克昂丹司琼口腔可溶性薄膜制剂的生物利用度。
本随机、开放标签、两期交叉研究在禁食条件下进行。总共10名符合条件的受试者按1:1比例随机分配，接受单次8毫克剂量的试验和参比昂丹司琼口腔可溶性薄膜制剂，随后经过1周的洗脱期并给予另一种制剂。使用液相色谱 - 质谱仪/质谱仪（LC-MS/MS）方法测定昂丹司琼的浓度。为分析药代动力学特性，包括达峰时间的峰浓度（Cmax）、从时间0（基线）至t小时的药时曲线下面积（AUC0-t）以及从基线至无穷大的药时曲线下面积（AUC0-∞），在研究药物给药后的24小时内间隔采集血样。通过监测生命体征和实验室检查（血液学、血液生化、肝功能和尿液分析）以及询问受试者不良事件来评估耐受性。
平均（标准差[SD]）相对生物利用度为96.5（23.7%）。Cmax和AUC0-t的对数转换比值的90%置信区间（CIs）分别为84.71% - 103.28%和91.38% - 108.60%（P>0.05）。未进行对数转换的数据也得到了类似结果。基于方差分析未发现统计学上的显著差异。研究期间未发生或报告显著不良事件。
由于基于试验制剂和参比制剂之间差异的90% CIs在Cmax和AUC0-t的80% - 125%范围内，我们得出结论，两种制剂在吸收速率或程度方面具有生物等效性。两种制剂耐受性良好。
