Degree of absorption, pharmacokinetics of fosfomycin trometamol and duration of urinary antibacterial activity

Abstract

The pharmacokinetics and in particular bioavailability of fosfomycin trometamol was studied and compared to the earlier emerging calcium salt formulation by administration of 50 mg/kg body weight orally of the two and an identical dose intravenously to all of eight healthy male volunteers. The serum and urine samples collected over 12 and 48 hours, respectively, were assayed microbiologically. The serum peak concentrations were 26.2 mg/l after trometamol and 6.5 mg/l after the calcium salt. Based on total area under the serum curves, the bioavailability of fosfomycin from the trometamol formulation was 42.3% compared to a mere 12% of the calcium salt. Urinary recovery was nearly completed within 12 hours, and the amounts eliminated in percentage of the doses were 87, 43, and 18% after the intravenous, the oral dose of trometamol and oral calcium salt, respectively. The serum half-life was 3.4 hours after intravenous administration, which demonstrates the inherent rate of elimination of fosfomycin. In comparison the half-life values were 3.6 hours after the trometamol dose, and 5.6 hours after the calcium salt. The longer elimination of the latter is explainable by the less complete absorption and consequent delayed absorption of fosfomycin from the calcium salt formulation. The antibacterial activity in urine upon administration of 50 mg/kg was prolonged to 48 hours in nearly all cases of trometamol orally and more than after the calcium salt orally or the sodium salt intravenously. A dose of 3 g for adults - or 50 mg/kg - is consistent with the findings in this study.