Accumulation of major linezolid metabolites in patients with renal impairment.

In patients with renal impairment (n=22 of 39), the median serum concentrations of linezolid, PNU-142300, and PNU-142586 were 1.6-, 3.3-, 2.8-fold higher for linezolid, PNU-142300 and PNU-142586, respectively, compared to patients without renal impairment. Metabolite concentrations in paired samples were poorly correlated to linezolid concentrations (r(2) = 0.26 for PNU-142300, and r(2)= 0.06 for PNU-142586). Linezolid and its metabolites share potential toxicophores that deserve characterization to mitigate higher myelosuppression risk in patients with renal impairment.