Source:Clinical Therapeutics
Author(s): Xiaojie Wu, Yunfei Li, Jing Zhang, Yingyuan Zhang, Jicheng Yu, Guoying Cao, Yuancheng Chen, Beining Guo, Yaoguo Shi, Jun Huang, Yuran Cao, Xiaofang Liu, Jufang Wu, Mikhail Fedorovich Gordeev, Hong Yuan, Wen Wang
PurposeThis study was designed to evaluate the safety and pharmacokinetic profiles of MRX-I tablet, an oxazolidinone antibacterial agent, in healthy Chinese subjects.MethodsThe study was composed of 3 sequential periods. Period 1 was a randomized, double-blind, placebo-controlled, sequential ascending dose (50 to 1800 mg) study. Period 2 included one arm as a randomized, open-label, 3-period, 3 × 3 Latin square single-dose study of 300, 600, and 900 mg MRX-I administration and another arm as a crossover study to evaluate high-fat diet effect. Period 3 was a randomized, double-blind, placebo-controlled multiple-dose study with 600 or 800 mg, q12h regimens over 15 days.FindingsMRX-I was rapidly absorbed and reached peak plasma concentration at about 2 hours post dose. The Cmax was 8.07, 12.24, and 15.25 mg/L and the corresponding AUC0−∞ 29.21, 48.27, and 59.60 mg/h/L, in 300-, 600-, and 900-mg dosing groups, respectively. High-fat diet increased the exposure of MRX-I. No discernable drug accumulation was observed after 15 days of continuous drug administration. About 2% of MRX-I was excreted via kidneys in unchanged form. No obvious hematologic toxicity by MRX-I was observed during the entire study. Based on Monte Carlo simulation, 600 or 800 mg BID can produce satisfactory efficacy against methicillin-resistant Staphylococcus aureus.ImplicationsMRX-I was well tolerated in healthy Chinese subjects (50–1800 mg). No serious or severe adverse effects were observed. MRX-I 600 or 800 mg BID up to 15 days can be recommended in future clinical trials. Chinese Clinical Trial Registration (http://ift.tt/1XFGNyx) identifier: CTR20131214.
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