Linezolid Population Pharmacokinetics to Improve Dosing in Cardiosurgical Patients: Factoring a New Drug–Drug Interaction Pathway.

This article focuses on optimizing linezolid dosing in adult cardiosurgical patients treated for serious gram-positive infections, addressing the drug's high interpatient pharmacokinetic variability and associated myelosuppression risk. A retrospective study of 150 patients revealed that the standard fixed dose of 600 mg every 12 hours often results in trough concentrations outside the therapeutic range (2–8 mg/L), with over 75% of patients requiring dose reductions. Population pharmacokinetic modeling identified kidney function and the number of concomitant interacting drugs—particularly cyclosporine, a CYP2J2 enzyme inhibitor—as significant factors reducing linezolid clearance. Simulations suggest empiric lower doses (300–450 mg every 12 hours) tailored to estimated glomerular filtration rate and co-medications may better achieve therapeutic levels, though therapeutic drug monitoring remains important for individualized dosing. The study highlights a novel metabolic pathway involving CYP2J2, predominantly expressed in cardiac tissue, as a potential mechanism for drug interactions affecting linezolid exposure in this population.