The effect of food on plasma and tissue concentrations of linezolid after multiple doses.

In the present pilot study we investigated the effect of food ingestion on target site pharmacokinetics of linezolid, the first clinically approved oxazolidinone. For this purpose we determined free concentrations of linezolid at steady state in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue under fasting and non-fasting conditions in healthy volunteers (n = 9) by means of in vivo microdialysis. Ingestion of food led to a marked delay in the time to reach the peak concentration (T(max)), whereas the area under the concentration-time curve from 0 to 24 h (AUC(0-24 h)) remained unchanged. These data suggest that the rate of linezolid absorption is decreased by food intake. However, the overall extent of linezolid absorption and the distribution of linezolid were not affected. Tissue levels of linezolid appeared sufficiently high to eradicate pathogens with a minimum inhibitory concentration of <or= 4 mg/L.