Transfer of latamoxef into human burn blister fluid and its pharmacokinetic analysis
Aoyama, H.; Sugiyama, H.; Suzuki, I.; Nishizaki, A.; Izawa, Y.; Oguma, T.; Yamada, H.
Japanese Journal of Antibiotics 38(10): 2821-2826
1985
ISSN/ISBN: 0368-2781 PMID: 4078995 Document Number: 258055
Latamoxef (LMOX) (50 mg/kg) was administrated intravenously to burned patients over 1 hour period. Burn blister fluid and serum were taken during 8 hours injection, and concentrations of LMOX in burn blister fluid and serum were determined by bioassay using Escherichia coli as a test organism. The serum concentrations of LMOX were 170.30.6 .mu.g/ml at 30 minutes, 227.0 .+-. 19.8 .mu.g/ml at 1 hour, 90.3 .+-. 21.4 .mu.g/ml at 2 hours, 52.9 .+-. 14.6 .mu.g/ml at 3 hours, 38.7 .+-. 13.3 .mu.g/ml at 4 hours, 25.1 .+-. 8.1 .mu.g/ml at 5 hours, 20.5 .+-. 8.1 .mu.g/ml at 6 hours, 13.0 .+-. 5.5 .mu.g/ml (mean .+-. S.D., n = 5) at 8 hours after the injection. The LMOX concentrations in burn blister fluid were 36.9 .+-. 32.8 .mu.g/ml at 30 minutes, 77.5 .+-. 42.2 .mu.g/ml at 1 hour, 85.4 .+-. 19.6 .mu.g/ml at 2 hours, 76.4 .+-. 18.5 .mu.g/ml at 3 hours, 63.5 .+-. 17.8 .mu.g/ml at 4 hours, 54.9 .+-. 17.1 .mu.g/ml at 5 hours, 34.8 .+-. 10.3 .mu.g/ml at 6 hours, 25.2 .+-. 4.8 .mu.g/ml (mean .+-. S.D., n = 7) at 8 hours after the injection. The data obtained were analysed pharmacokinetically. The serum levels were analysed by two-compartment model, and the LMOX levels in burn blister fluid were analysed by the model, in which blister was considered as a small part of the peripheral compartment. In results, Tmax and Cmax of LMOX levels in burn blister fluid were calculated as 1.81 hours and 90.6 .mu.g/ml, respectively. The transfer rate constant of LMOX from serum to burn blister fluid shown as a hyblid parameter-K13 (transfer rate constant from serum to burn blister fluid) divided with V3 (volume of burn blister fluid)-was 12.25 hr-1 .cntdot. kg/L. The transfer rate constant of LMOX from burn blister fluid to serum (K31) was 0.61 hr-1.