Dai Jun, Zhou Yanan, Zhang Lei, Ren Qing, Liu Zhengzhi, Wang Yanli, Cheng Yang, Deng Qiaohuan, Yang Haimiao, Zhang Hong
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China.
Front Pharmacol. 2025 May 30;16:1586368. doi: 10.3389/fphar.2025.1586368. eCollection 2025.
The purpose of this study was to evaluate the food effect on the pharmacokinetics of TQB3616 capsule in Chinse healthy subjects.
The subjects were randomly allocated to two distinct sequences in a 1:1 ratio. During each treatment periods, subjects ingested a single oral dose of 180 mg TQB3616 capsule administered with 240 mL of warm water under fasted and fed conditions. To avoid carryover effects, a 19 days washout period was strictly implemented between treatment periods. Blood samples were collected in accordance with the study protocol, and the plasma concentration of TQB3616 was measured using a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Safety evaluations were performed continuously throughout the duration of the trial.
Following the administration of TQB3616 capsules under both fasted and fed conditions, the geometric mean ratios of C, AUC, and AUC0- for TQB3616 in the fed state compared to the fasted state were 148.04%, 145.06%, and 143.13%, respectively. The corresponding 90% confidence intervals (CIs) were 101.23%-216.51%, 117.68%-178.83%, and 116.46%-175.91%, none of which fell within the conventional bioequivalence range of 80.00%-125.00%. A total of 81 adverse events (AEs) were reported among 16 subjects, with 77 events deemed related to the drug. Among the 77 drug-related adverse events, two cases were grade II, with the rest being grade I. Notably, there were no serious adverse events, deaths, or unexpected serious reactions.
A pharmacokinetic study conducted on healthy volunteers, who received a single 180 mg dose of TQB3616 capsules under fasting and fed conditions, demonstrated clinically significant effects of food on the drug's bioavailability. Compared with fasted, postprandial administration delayed median T by 1 h while increasing total systemic exposure and peak concentration. Additionally, postprandial dosing was associated with reduced incidence of gastrointestinal adverse reactions. These data support the recommendation that TQB3616 capsules be administered with food to maximize therapeutic bioavailability while improving gastrointestinal tolerability profile.
http://www.chinadrugtrials.org.cn, identifier, CTR20210354; clinicaltrials.gov, identifier, NCT05344729.
本研究旨在评估食物对TQB3616胶囊在中国健康受试者体内药代动力学的影响。
受试者按1:1比例随机分配至两个不同序列。在每个治疗期，受试者在禁食和进食条件下，用240 mL温水送服180 mg TQB3616胶囊单剂量口服。为避免残留效应，治疗期之间严格执行19天的洗脱期。根据研究方案采集血样，采用经过充分验证的液相色谱-串联质谱（LC-MS/MS）法测定TQB3616的血浆浓度。在整个试验期间持续进行安全性评估。
在禁食和进食条件下服用TQB3616胶囊后，进食状态下TQB3616的C、AUC和AUC0- 的几何平均比值与禁食状态相比分别为148.04%、145.06%和143.13%。相应的90%置信区间（CIs）分别为101.23%-216.51%、117.68%-178.83%和116.46%-175.91%，均未落在80.00%-125.00%的传统生物等效性范围内。16名受试者共报告81例不良事件（AEs），其中77例被认为与药物有关。在77例与药物相关的不良事件中，2例为II级，其余为I级。值得注意的是，未发生严重不良事件、死亡或意外严重反应。
对健康志愿者在禁食和进食条件下单次服用180 mg剂量TQB3616胶囊进行的药代动力学研究表明，食物对该药物的生物利用度具有临床显著影响。与禁食相比，餐后给药使T的中位数延迟1小时，同时增加了全身总暴露量和峰浓度。此外，餐后给药与胃肠道不良反应发生率降低有关。这些数据支持以下建议：服用TQB3616胶囊时应与食物同服，以最大化治疗性生物利用度，同时改善胃肠道耐受性。
http://www.chinadrugtrials.org.cn，标识符，CTR20210354；clinicaltrials.gov，标识符，NCT05344729。
