Linezolid in the central nervous system: comparison between cerebrospinal fluid and plasma pharmacokinetics.

Abstract

BACKGROUND:

Linezolid is effective against methicillin-resistant Staphylococcus aureus, which may cause central nervous system (CNS) infections, but drug concentrations in plasma are characterized by a large inter-patient variability. Therefore, the present study was aimed at evaluating linezolid pharmacokinetics in plasma and cerebrospinal fluid (CSF) in 7 patients with external ventricular drainage, who received linezolid 600 mg twice daily as 1-h intravenous infusion to prevent CNS infections.

METHODS:

Plasma and CSF linezolid concentrations were measured by high-performance liquid chromatography (HPLC) after the 1(st) and 5(th) dose, and pharmacokinetics were evaluated by non-compartmental analysis.

RESULTS:

Values of the CSF area under the time/concentration curve (AUC) (range 18.2-85.5 and 19.6-160.5 h × mg/l at the 1st and 5th dose, respectively) were lower than those calculated in plasma (range 27.6-224.0 and 27.5-166.1 h × mg/l, respectively). For minimum inhibitory concentration (MIC) = 1 mg/l, CSF AUC/MIC values were nearly equal to or greater than 100 only in 2 subjects after the 1st and 5th dose, whereas mean time above the MIC (T > MIC) values were higher than 75% in only 3 patients. Similar results were obtained when pharmacokinetic/pharmacodynamic parameters were evaluated in plasma.

CONCLUSION:

The present results suggest that changes in linezolid doses and measurement of drug concentrations should be considered as useful strategies to optimize treatment in some patients.

• Authors: Bruno Viaggi, Antonello Di Paolo, Romano Danesi, Marialuisa Polillo, Laura Ciofi, Mario Del Tacca, Paolo Malacarne
• Journal: Scandinavian journal of infectious diseases (Scand J Infect Dis) Vol. 43 Issue 9 Pg. 721-7 (Sep 2011) ISSN: 1651-1980 [Electronic] England
• PMID: 21585240 (Publication Type: Journal Article)

Chemical References

• Acetamides
• Anti-Bacterial Agents
• Oxazolidinones
• Linezolid

Topics

• Acetamides (administration & dosage, pharmacokinetics)
• Adult
• Aged
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Bacterial Infections (prevention & control)
• Cerebrospinal Fluid (chemistry)
• Cerebrospinal Fluid Shunts
• Chromatography, High Pressure Liquid
• Female
• Humans
• Infusions, Intravenous
• Linezolid
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Oxazolidinones (administration & dosage, pharmacokinetics)
• Plasma (chemistry)
• Time Factors