Advances in Therapeutic Drug Monitoring and Pharmacokinetic Researches of Oxazolidinone Antibacterial Agents in the Elderly Patients

Background: Elderly patients are at increased risk of infection with methicillin-resistant Staphylococcus aureus (MRSA). Therefore, this article comprehensively reviews the progress in therapeutic drug monitoring (TDM) and pharmacokinetic (PK) studies of linezolid, contezolid and tedizolid in the elderly population, to inform individualized dosing strategies. Methods: This review synthesized evidence from published and ongoing studies examining the TDM and PK studies of linezolid, contezolid and tedizolid in elderly patients, encompassing investigations into drug concentrations monitoring, PK parameters, and population PK studies. No date restrictions were applied to the study selection. Results: The distinct pathophysiology of elderly patients leads to significant alterations in the PK characteristics of various antibacterial agents, necessitating individualized dosage adjustments. In this population, linezolid exhibits a prolonged half-life, markedly decreased clearance, and elevated risk of severe overexposure. Therefore, its dosage requires adjustment based on renal function and age. Contezolid exhibits comparable pharmacokinetics in patients aged 65– 74 years to younger adults; however, in patients aged 80 and above, its time to peak concentration is delayed, elimination is accelerated, while C max and AUC 0-t increase dose-dependently. Tedizolid plasma exposure was similar in elderly and younger control subjects, indicating that no dose adjustment was warranted for elderly subjects. Moreover, contezolid and tedizolid exhibit a more favorable safety profile compared with linezolid. Conclusion: The PK characteristics of oxazolidinone antibiotics may be altered in the elderly population. TDM and model-informed precision dosing (MIPD) are crucial approaches for achieving individualized dosing strategies. Keywords: oxazolidinone antibacterial agents, therapeutic drug monitoring, pharmacokinetics, population pharmacokinetic model, elderly patients