This means that people receiving intravenous linezolid may be switched to oral linezolid as soon as their condition allows it, whereas comparable antibiotics (such as vancomycin and quinupristin/dalfopristin) can only be given intravenously. Taking linezolid with food somewhat slows its absorption, but the area under the curve is not affected.Linezolids plasma protein binding is approximately 31% (range 4–32%) and its volume of distribution at steady state averages 36.1–47.3 liters in healthy adult volunteers. Peak plasma concentrations (Cmax) are reached one to two hours after administration of the drug. Linezolid is readily distributed to all tissues in the body apart from bone matrix and white adipose tissue. Notably, the concentration of linezolid in the epithelial lining fluid (ELF) of the lower respiratory tract is at least equal to, and often higher than, that achieved in serum (some authors have reported bronchial fluid concentrations up to four times higher than serum concentrations), which may account for its efficacy in treating pneumonia. However, a meta-analysis of clinical trials found that linezolid was not superior to vancomycin, which achieves lower concentrations in the ELF. Cerebrospinal fluid (CSF) concentrations vary; peak CSF concentrations are lower than serum ones, due to slow diffusion across the blood–brain barrier, and trough concentrations in the CSF are higher for the same reason. The average half-life is three hours in children, four hours in teenagers, and five hours in adults.Linezolid is metabolized in the liver, by oxidation of the morpholine ring, without involvement of the cytochrome P450 system.
This metabolic pathway leads to two major inactive metabolites (which each account for around 45% and 10% of an excreted dose at steady state), one minor metabolite, and several trace metabolites, none of which accounts for more than 1% of an excreted dose. Clearance of linezolid varies with age and gender; it is fastest in children (which accounts for the shorter half-life), and appears to be 20% lower in women than in men. There is a strong correlation between linezolid clearance and creatinine clearance. Chemistry
At physiological pH (7.4), linezolid exists in an uncharged state. It is moderately water-soluble (approximately 3 mg/mL), with a logP of 0.55. The oxazolidinone pharmacophore—the chemical "template" essential for antimicrobial activity—consists of a 1,3-oxazolidin-2-one moiety with an aryl group at position 3 and an S-methyl group, with another substituent attached to it, at position 5 (the R-enantiomers of all oxazolidinones are devoid of antibiotic properties). In addition to this essential core, linezolid also contains several structural characteristics that improve its effectiveness and safety. An acetamide substituent on the 5-methyl group is the best choice in terms of antibacterial efficacy, and is used in all of the more active oxazolidinones developed thus far; in fact, straying too far from an acetamide group at this position makes the drug lose its antimicrobial power, although weak to moderate activity is maintained when some isosteric groups are used.