[Pharmacokinetic evaluation of linezolid in patients with major thermal injuries].
The aims of this multicentre open-label study was to evaluate the pharmacokinetics of linezolid in patients with burn injury above 20 % BSA and to compare them with healthy volunteers, matched in age, sex and weight. After a single 600 mg IV dose of linezolid, multiple blood and urine samples were taken from subjects, in order to determine linezolid concentrations, using a HPLC assay. C(max) and volume of distribution at steady state were not different between the two groups. Values describing clearance were altered in burns, leading to a reduction by half in AUC in these patients (42.5 versus 98.1 mghL(-1)). The enhancement of clearance was due to which of non renal clearance (323+/-191 versus 80.4+/-27.5 mLmin(-1)). We conclude that pharmacokinetics of linezolid are altered in burn patients, in a magnitude sufficient that linezolid concentration may be subtherapeutic in some patients and we suggest that the dosage interval may need to be decreased in this patient population.
Le Floch
R
R
Centre de traitement des brûlés, CHU de Nantes, 44093 Nantes cedex 1, France. ronan.lefloch@chu-nantes.fr
Arnould
J-F
JF
Vinsonneau
C
C
Hovsepian
L
L
Stephanazzi
J
J
Bret
P
P
Birraux
G
G
Lovering
A M
AM
D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D019540:Area Under Curve; D002056:Burns / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D055815:Young Adult
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid