Linezolid pharmacokinetics: a systematic review for the best clinical practice

To summarize the pharmacokinetics of linezolid to optimize the dosing regimen in special populations.

A literature search was performed in three largest medical databases, including Embase, Scopus, and PubMed. The main applied keywords were linezolid and pharmacokinetics. Of 3663 retrieved publications in the English language, 35 original research articles, clinical studies, and case reports about linezolid pharmacokinetics in different populations such as pregnant women, pediatrics, elderly subjects, obese people, individuals with organ dysfunction, and critically ill patients were included. RESULTS AND CONCLUSION: Dose adjustment is not currently recommended for linezolid in patients with mild to moderate renal or hepatic impairment, older adults, and pregnant women. Although dose adjustment is not recommended in patients with severe renal or hepatic impairment, it should be considered that these patients are more vulnerable to linezolid adverse effects and drug interactions. In pediatrics, reducing the linezolid dosing interval to 8 h is suggested. Despite the lack of sufficient information in obese individuals, dosing based on body weight or use of higher dose seems to be justifiable to prevent sub-therapeutic concentrations. Although dose adjustment of linezolid is not recommended in critically ill patients, administration of linezolid as continuous intravenous infusion is suggested in this population. Blood level monitoring should be considered in populations that are vulnerable to linezolid underexposure (such as critically ill patients with augmented renal clearance, pediatrics, overweight, and obese patients) or overexposure (such as elderly, patients with hepatic and renal impairment). To assess the efficacy and safety of linezolid, the area under the concentration-time curve over 24 h to minimum inhibitory concentration (AUC0-24 h/MIC) equal to 80-120, percentage of time above the MIC ≥ 85%, and serum trough concentration between 2 and 7 mg/L are suggested.