Short-term Safety, Tolerability, and Pharmacokinetics of MRX-I, an Oxazolidinone Antibacterial Agent, in Healthy Chinese Subjects
In: Clinical Therapeutics, Jg. 40 (2018-02-01), S. 322-322
Online
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Zugriff:
Purpose This study was designed to evaluate the safety and pharmacokinetic profiles of MRX-I tablet, an oxazolidinone antibacterial agent, in healthy Chinese subjects. Methods The 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. Findings MRX-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. Implications MRX-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://www.chinadrugtrials.org.cn ) identifier: CTR20131214.
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Short-term Safety, Tolerability, and Pharmacokinetics of MRX-I, an Oxazolidinone Antibacterial Agent, in Healthy Chinese Subjects
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Autor/in / Beteiligte Person: | Li, Yunfei ; Liu, Xiao-fang ; Wu, Xiaojie ; Zhang, Yingyuan ; Chen, Yuancheng ; Yu, Jicheng ; Wang, Wen ; Cao, Yuran ; Shi, Yaoguo ; Guo, Beining ; Mikhail Fedorovich Gordeev ; Wu, Jufang ; Yuan, Hong ; Zhang, Jing ; Huang, Jun ; Cao, Guoying |
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Zeitschrift: | Clinical Therapeutics, Jg. 40 (2018-02-01), S. 322-322 |
Veröffentlichung: | Elsevier BV, 2018 |
Medientyp: | unknown |
ISSN: | 0149-2918 (print) |
DOI: | 10.1016/j.clinthera.2017.12.017 |
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