Linearity of the pharmacokinetics of phosphomycin in serum and interstitial tissue fluid in rabbits.

A study was carried out on the access and residence of (-)(1R,2S)-1,2-epoxypropylphosphonic acid (phosphomycin) in interstitial tissue fluid produced experimentally by subcutaneous implantation of spiral steel cages after administration of doses of 20, 30 and 60 mg/kg of the antibiotic to rabbits. The levels reached by the drug in serum and interstitial tissue fluid (ITF) were determined by a microbiological plate diffusion method. The elimination half-lives of phosphomycin ranged between 1.16 and 1.57 h. These values are similar to those found for the disappearance half-lives from ITF. Phosphomycin reached maximum concentrations in ITF between 31.95 and 80.37 micrograms/ml. Linear relationships were established between the (AUC) 0 infinity in serum, the (AUC) 0 infinity in ITF and Cmax in ITF and the doses studied, revealing the non-dose-dependent kinetics of phosphomycin. The linearity of phosphomycin kinetics was checked in serum and ITF by applying the superposition principle.