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

• Published in: Antimicrobial agents and chemotherapy Vol. 66; no. 6; p. e0243021
• Main Authors: Yuan, Hong, Wu, Hailan, Zhang, Yingyuan, Huang, Haihui, Li, Yi, Wu, Junzhen, Cao, Guoying, Yu, Jicheng, Guo, Beining, Wu, Jufang, Yuan, Zhengyu, Chen, Yuancheng, Yang, Wanqiu, Wu, Xiaojie, Zhang, Jing
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 21.06.2022
• Subjects: Antimicrobial Chemotherapy; Pharmacology; contezolid; exposure; pharmacokinetic/pharmacodynamic analysis; population pharmacokinetics
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.02430-21

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. 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 postprandially for 7 to 14 days is expected to achieve satisfactory clinical and microbiological efficacy in cSSTIs, which is slightly better than that of 600 mg contezolid. This administration has been added to the prescribing information of contezolid tablets.