Sunwoo Jung, Kim Yu Kyong, Choi Yewon, Yu Kyung-Sang, Nam Heesook, Cho Young Lag, Yoon Seonghae, Chung Jae-Yong
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul.
LegoChem Biosciences, Inc., Daejeon.
Drug Des Devel Ther. 2018 Jun 11;12:1707-1714. doi: 10.2147/DDDT.S155657. eCollection 2018.
LCB01-0371 is a novel oxazolidinone antibiotic that blocks protein production by binding to bacterial 23S ribosomes. This antibiotic is active against Gram-positive bacteria. This study aimed to evaluate the effect of food on the pharmacokinetics (PKs) of LCB01-0371 and evaluate its safety profile.
A randomized, open-label, two-way crossover study was performed in 18 healthy Korean male subjects. All subjects received a single oral 800 mg dose of LCB01-0371 in each period under fed or fasting condition with a 7-day washout in between. The fed condition was defined as consumption of a meal of 800-1,000 kcal containinĝ50% of fat content. Serial blood samples were collected over 24 h after dosing, and the PK parameters were calculated by noncompartment analysis. All available data of the subjects who received LCB01-0371 at least once were included in the safety data summaries.
In the fed condition, both the maximum plasma concentration () and the total systemic exposure (area under the plasma concentration-time curve from time zero to the last observed time point [AUC]) decreased by ~33% and 10%, respectively. The time to reach was delayed by ~1.25 h in the fed condition, whereas the mean elimination half-life remained similar in both conditions. In the fed/fasting condition, the geometric mean ratios and 90% CI of the and AUC were 0.666 (0.470-0.945) and 0.897 (0.761-1.057), respectively. There were no drug-related adverse events (AEs) or serious AEs.
Although the after a single oral 800 mg dose of LCB01-0371 was slightly delayed under the fed condition compared to the fasting condition, the total systemic exposure was similar under both conditions. Therefore, LCB01-0371 could be administered regardless of food intake.
LCB01-0371是一种新型恶唑烷酮类抗生素，通过与细菌23S核糖体结合来阻断蛋白质合成。这种抗生素对革兰氏阳性菌具有活性。本研究旨在评估食物对LCB01-0371药代动力学（PKs）的影响，并评估其安全性。
在18名健康韩国男性受试者中进行了一项随机、开放标签、双向交叉研究。所有受试者在每个时间段分别在进食或禁食条件下接受单次口服800 mg剂量的LCB01-0371，中间间隔7天的洗脱期。进食条件定义为摄入含50%脂肪含量、800-1000千卡的一餐。给药后24小时内采集系列血样，通过非房室分析计算PK参数。接受过至少一次LCB01-0371的受试者的所有可用数据均纳入安全性数据总结。
在进食条件下，最大血浆浓度（）和全身总暴露量（从时间零点到最后观察时间点的血浆浓度-时间曲线下面积[AUC]）分别降低了约33%和10%。进食条件下达到的时间延迟了约1.25小时，而两种条件下的平均消除半衰期保持相似。在进食/禁食条件下，和AUC的几何平均比值及90%置信区间分别为0.666（0.470-0.945）和0.897（0.761-1.057）。未出现与药物相关的不良事件（AE）或严重AE。
尽管单次口服800 mg剂量的LCB01-0371后，进食条件下的比禁食条件下略有延迟，但两种条件下的全身总暴露量相似。因此，无论是否进食，均可给予LCB01-0371。
