Wang Jingyan, Xu Yuan, Zhao Zhicheng, Meng Tian, Zou Yang, Lan Yi
College of Health Industry, Sichuan Tourism University, Chengdu, Sichuan, China.
Qingdao Fifth People's Hospital, Qingdao, Shandong, China.
Clin Pharmacol Drug Dev. 2025 Feb;14(2):177-183. doi: 10.1002/cpdd.1490. Epub 2024 Nov 25.
The aim of this study was to investigate the pharmacokinetics, bioequivalence, and safety of generic trazodone hydrochloride sustained-release tablet and its reference listed product in healthy Chinese subjects. An open, randomized, single-dose, and 2-period crossover study was involved under fasting and fed conditions, with a 7-day washout period. A single oral dose of 150 mg of 2 trazodone hydrochloride sustained-release tablets was administered to 84 healthy volunteers, with 36 in the fasting group and 48 consuming a high-fat diet, respectively. The plasma concentrations of trazodone were analyzed using a liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were obtained from concentration-time profiles. The geometric mean ratio with 90% confidence intervals of the maximum trazodone concentration, area under the plasma concentration-time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the bioequivalence acceptance criteria (80%-125%) under fasting and fed conditions, which indicated that the test and reference formulations were bioequivalent. Compared with the fasting study, the concomitant administration of trazodone with a high-fat diet had a negligible influence on the drug pharmacokinetic behavior. Adverse events were recorded, and no serious adverse events were observed during either fasting or fed conditions. Trazodone has proven to have an acceptable safety profile in the Chinese population, with bioequivalence successfully established under both fasting and fed conditions.
本研究旨在考察国产盐酸曲唑酮缓释片及其参比制剂在健康中国受试者中的药代动力学、生物等效性和安全性。采用开放、随机、单剂量、两周期交叉试验设计,试验在空腹和进食条件下进行,洗脱期为7天。84名健康志愿者分别单次口服150 mg两种盐酸曲唑酮缓释片,其中36名处于空腹组,48名进食高脂饮食。采用液相色谱 - 串联质谱法分析曲唑酮血浆浓度,并从浓度 - 时间曲线获得药代动力学参数。空腹和进食条件下,曲唑酮最大浓度、血浆浓度 - 时间曲线下面积(AUC)从0至最后可测浓度、AUC从0至无穷大的几何平均比值及其90%置信区间均在生物等效性接受标准(80% - 125%)范围内,表明受试制剂与参比制剂生物等效。与空腹研究相比,曲唑酮与高脂饮食同时服用对药物药代动力学行为的影响可忽略不计。记录不良事件,空腹和进食条件下均未观察到严重不良事件。结果证明,曲唑酮在中国人群中具有可接受的安全性,在空腹和进食条件下均成功建立了生物等效性。