fosfomycin and Burns

The pharmacokinetics of fosfomycin are modified in burn patients, suggesting a net tubular secretion in such patients. In an attempt to verify this hypothesis, five healthy normal volunteers were studied The pharmacokinetics of fosfomycin were studied with and without probenecid. In the absence of probenecid, the renal clearance of the drug was equal to that of creatinine. With probenecid, the renal clearance of fosfomycin decreased, whereas creatinine clearance did not. This result suggests the existence of a tubular secretion, which might be enhanced in burn patients.

Topics: Adult; Burns; Drug Interactions; Fosfomycin; Half-Life; Humans; Infusions, Intravenous; Probenecid

Fosfomycin (FOM) (50 mg/kg) was administered to burned patients by intravenous bolus injection. Burn blister fluid and serum were taken during 8 hours after injection, and concentrations of FOM in burn blister fluid and serum were determined by bioassay using Proteus sp. (MB-838) as the test organism. The serum concentrations of FOM were 257 +/- 34.6 micrograms/ml at 15 minutes, 222 +/- 34.8 micrograms/ml at 30 minutes, 166 +/- 34.6 micrograms/ml at 1 hour, 114 +/- 43.9 micrograms/ml at 2 hours, 79.5 +/- 34.9 micrograms/ml at 3 hours, 63 +/- 36.4 micrograms/ml at 4 hours, 44.3 +/- 27.6 micrograms/ml at 5 hours, 29.6 +/- 20.9 micrograms/ml at 6 hours and 17.9 +/- 12.8 micrograms/ml at 8 hours after the injection. FOM concentrations in burn blister fluid were 64.4 +/- 18.1 micrograms/ml at 30 minutes, 77 +/- 26.0 micrograms/ml at 1 hour, 71.6 +/- 24.7 micrograms/ml at 2 hours, 64.8 +/- 23.6 micrograms/ml at 3 hours, 43.2 +/- 8.8 micrograms/ml at 4 hours, 24.8 +/- 7.9 micrograms/ml at 6 hours and 17.9 +/- 10.5 micrograms/ml at 8 hours after the injection. The obtained data were analysed pharmacokinetically. The serum levels were analysed by a two-compartment model, and the transfer of FOM into burn blister was analysed by a modified deconvolution method. In results, Tmax and Cmax of FOM levels in burn blister fluid were calculated as 1.3 hours and 80.9 micrograms/ml, respectively. The transfer rate constant of FOM from serum to burn blister fluid (K1) and that from burn blister fluid to serum (K2) were calculated as 0.612 hr-1 and 1.10 hr-1, respectively.

Topics: Adult; Aged; Blister; Burns; Exudates and Transudates; Fosfomycin; Humans; Injections, Intravenous; Kinetics; Middle Aged

Topics: Burns; Catheterization; Child; Fosfomycin; Humans; Male; Mediastinum; Parenteral Nutrition; Skin Transplantation; Staphylococcal Infections; Subclavian Vein