DISCUSSION
retinopathy, gastrointestinal symptoms, swelling, leukopenia, thrombocytopenia, TEAEs, anemia, SAD, pain, paraesthesia, deaths, nausea, vomiting
ADVERSE REACTIONS, RETINOPATHY, CLINICAL INFECTIONS, LEUKOPENIA, THROMBOCYTOPENIA, ANEMIA, PARAESTHESIA, PANCYTOPENIA
The primary objective of this study was to evaluate the safety, tolerability, and PK profiles of contezolid acefosamil in healthy Chinese adults. Overall, contezolid acefosamil was well-tolerated after IV or oral SAD and multiple doses. All TEAEs were mild and resolved spontaneously without discontinuation or treatment. No deaths, SAEs, severe AEs, or AEs leading to early withdrawal were reported.After oral administration of contezolid acefosamil, the incidence of study drug-related AEs increased with single-dose escalation and multiple doses (80.0% in multiple-dose cohort and 11.1% in single-dose cohorts). The most common study drug-related AEs in the oral cohorts were gastrointestinal symptoms, including nausea, vomiting, and abdominal distension, which are consistent with the known AEs of oxazolidinone drugs (The results of this study indicate that the safety, tolerability, and PK characteristics of oral contezolid acefosamil are similar to those of contezolid (Drug-related AEs were less common with IV contezolid acefosamil (11.1%) compared with contezolid acefosamil tablets (47.4%), especially in gastrointestinal symptoms. In addition, drug-related AEs did not tend to increase with IV dose escalation or multiple doses. There is no infusion site pain, swelling, or paraesthesia reported in this study, which were the most common AEs in the phase I trial of tedizolid injection (The typical adverse reactions which limit the clinical use of oxazolidinone antibiotics include thrombocytopenia, leukopenia, pancytopenia, and anemia. Tedizolid, as a second-generation oxazolidinone antibiotic, may also cause thrombocytopenia after 6-day treatment (Since long-term use of linezolid can cause retinopathy (In this study, the parent drug contezolid acefosamil was only measured in the IV SAD cohorts because contezolid acefosamil concentration was below the lower limit of quantitation at all sampling time points in all of the oral cohorts according to the results of the phase I study in the US. The plasma concentrations of metabolites increased with the IV dose of contezolid acefosamil. The parent drug contezolid acefosamil was undetectable At an equivalent dose of 500 mg, the mean ratio of the AUCConsidering that contezolid acefosamil injection is a different dosage form important for the patients with severe clinical infections or those who cannot tolerate oral administration, a popPK model of contezolid acefosamil injection in healthy Chinese subjects was constructed. In addition to the data of the IV cohorts in this study, the model also included the relevant data in the second cycle of 2,000-mg single-dose IV cohort (2,000/1,000 mg). The factors affecting the PK of contezolid acefosamil injection were preliminarily examined in the model to support the subsequent development of contezolid acefosamil. This study found that body weight had significant effect on CL, and other covariates had no significant effect on the exposure of contezolid acefosamil injection.