Clinical Pharmacology and Utility of Contezolid in Chinese Patients with Complicated Skin and Soft-Tissue Infections

作者：Hong Yuan, Hailan Wu, Yingyuan Zhang, Haihui Huang, Yi Li, Junzhen Wu, Guoying Cao, Jicheng Yu, Beining Guo, Jufang Wu, Zhengyu Yuan, Yuancheng Chen, Wanqiu Yang, Xiaojie Wu, Jing Zhang · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2022 · DOI：10.1128/aac.02430-21 · 被引用次数：14 · 研究领域：Antimicrobial Resistance in Staphylococcus、Antibiotics Pharmacokinetics and Efficacy、Antibiotic Resistance in Bacteria

This study aimed to build a population pharmacokinetic (PopPK) model for contezolid tablet (MRX-I) in healthy subjects and adults with complicated skin and soft-tissue infections (cSSTIs) to further evaluate the efficacy and safety of contezolid and recommend the optimal dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. PopPK analysis was performed using a nonlinear mixed-effects model (NONMEM) to examine the effects of age, body weight, sex, liver and renal functions, albumin, food, dosage strength, and subject type on the PK parameters of contezolid. PK/PD analysis was combined with the MIC of contezolid, clinical/microbiological efficacy, and nonclinical study data. Adverse events (AEs) and study drug-related AEs reported were summarized to examine the relationship between contezolid exposure level and safety measures. A two-compartment model was built. An exponential model was used to describe the interindividual variation. A proportional model was used to describe the intraindividual variation of PK parameters. Good clinical and microbiological efficacy are expected for the infections caused by S. aureus when contezolid is administered at 600 mg or 800 mg every 12 h (q12h). The area under the concentration-time curve from 0 to 24 h at steady state and maximum concentration of drug in serum at steady state of contezolid did not show significant association with the incidence of any AE. The dosing regimen of contezolid at 800 mg q12h administered po...