Penetration of Contezolid into bone tissues and body fluids in patients undergoing artificial hip or knee replacement...

This study aimed to examine the pharmacokinetic (PK) characteristics and penetration of contezolid into bone tissues and body fluids in patients undergoing artificial hip or knee replacement surgery.

In a prospective, single center, open label, cohort study, patients received 800 mg contezolid tablets orally, twice a day, for at least two days before surgery. The steady-state PK parameters of contezolid in plasma, body fluids and bone tissues were determined using both noncompartmental analysis (NCA) and population pharmacokinetic (PopPK) modeling.

The plasma peak concentration (C_max) of contezolid was 7.25 ± 5.27 mg/L in 6 patients undergoing hip replacement surgery, while the corresponding value was 11.46 ± 6.48 mg/L in 15 patients undergoing knee replacement. The median time to maximum plasma concentration (T_max) was 1 hour after multiple oral doses of 800 mg contezolid. The ratio of the area under the concentration-time curve of contezolid from 0-12 h (AUC_0-12h,ss) in tissue to the AUC_0-12h,ss in plasma was 0.39 to 1.34 in patients undergoing hip replacement surgery, with body fluid-to-plasma AUC_0-12h,ss ratio was 0.69. In patients undergoing knee replacement, the tissue-to-plasma AUC_0-12h,ss ratio was 0.12-0.56 and body fluid-to-plasma AUC_0-12h,ss ratio was 0.51.

The penetration of contezolid into bone and joint tissues can justify the utility of contezolid in managing infections during joint replacement surgery.

http://www.chinadrugtrials.org.cn/ (identifier: CTR20230232）.