Linezolid absolute bioavailability and the effect of food on oral bioavailability

Linezolid is a novel oxazolidinone antibiotic that has a spectrum of activi ty encompassing a variety of Gram-positive bacteria. The objectives of this study were twofold: (1) to compare the absorption of linezolid tablets giv en immediately following a high-fat meal with the absorption of tablets adm inistered While fasting, and (2) to assess the bioavailability of a 375-mg oral dose given while fasting relative to a 375-mg dose of linezolid steril e solution given intravenously. Venous blood samples were taken over the 48 h following the single dose administration of both the oral and intravenou s (IV) treatment. Samples were subsequently frozen for the determination of linezolid concentrations by HPLC. The only statistically significant diffe rence between the fasted and the fed treatment was in peak plasma concentra tion, with the mean C-max for fasted subjects being 23% greater than that f or subjects after consumption of a high-fat meal. Comparable AUC(0-infinity ) values were measured under both conditions, indicating that the overall e xtent of absorption is the same. Therefore, the difference in C-max, while statistically significant, should not affect the therapeutic efficacy of li nezolid when it is administered with food. There were no statistically sign ificant differences in AUC(0-infinity), CL or half-life between the fasted oral treatment and the intravenous treatment. As expected, C-max was statis tically different between the two treatments. However, the mean absolute bi oavailability (F) of the tablet, using the IV sterile solution as the refer ence treatment, was 103%(+/- 20%). Copyright (C) 2001 John Wiley & Sons, Lt d.