[Transfer of fosfomycin into human burn blister fluid and its pharmacokinetic analysis]

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.