[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.
Centre de traitement des brûlés, CHU de Nantes, 44093 Nantes cedex 1, France. ronan.lefloch@chu-nantes.fr
R
R
Le Floch
J-F
JF
Arnould
C
C
Vinsonneau
L
L
Hovsepian
J
J
Stephanazzi
P
P
Bret
G
G
Birraux
A M
AM
Lovering
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