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    上海強世信息科技有限公司

    Concentration-response modeling of ECG data from early-phase clinical studies to assess QT prolongation risk of contezolid (MRX-I), an oxazolidinone antibacterial agent.
    作者: | 發(fā)布:Wu Junzhen,Wang Kun,Chen Yuancheng,Yuan Hong,Li Li,Zhang Jing. | 發(fā)布時間: 2019-12-01 | 316 次瀏覽 | 分享到:
    The effects of contezolid (MRX-I, an oxazolidinone antibacterial agent) on cardiac repolarization were evaluated retrospectively using a population modeling approach in a Phase I study incorporating single ascending dose, multiple ascending dose, and food effect assessments. Linear mixed effect models were used to assess the relationships between MRX-I plasma concentrations and QT/QTc/?QTc (baseline-adjusted), in which different correction methods for heart rate have been included. The upper bound of the one-sided 95% confidence interval (CI) for predicted ??QTc was < 10 ms (ms) at therapeutic doses of MRX-I. Model performance/suitability was determined using diagnostic evaluations, which indicated rationality of one-stage concentration-QT model, as well as C-QT model suggested by Garnett et al. The finding demonstrated that MRX-I may have no clinical effects on the QT interval. Concentration-QT model may be an alternative to conventional thorough QT studies.

    [J]. Journal of pharmacokinetics and pharmacodynamics,2019 Jan,46(6)

    https://pubmed.ncbi.nlm.nih.gov/31410633/

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