Cefodizime in serum and skin blister fluid after single intravenous and intramuscular doses in healthy volunteers

Abstract

In gonorrhea therapy, cephalosporins are conventionally administered by intramuscular (i.m.) injection, which rather frequently leads to local side effects. To investigate whether the well-tolerated intravenous (i.v.) injection of cephalosporins may be of comparable gonocidal effect, levels of cefodizime, a new broad-spectrum cephalosporin, in serum and tissue fluid (suction blister and cantharides blister fluid) were determined in six healthy men. Single doses of 1 g of cefodizime were injected i.v. and i.m. according to a randomized crossover design. On i.m. injection the drug was completely bioavailable, and the peak concentration in serum was 75 +/- 8 micrograms/ml. The terminal half-life of serum levels was 2.4 h. Cefodizime concentrations in the blister fluids increased for 1.5 to 3 h after the i.v. dose and for at least 3 h on i.m. administration. The concentrations of non-protein-bound cefodizime in blister fluid already exceeded the MIC for 90% of Neisseria gonorrhoeae strains 10 min after i.v. injection and 20 to 30 min after the i.m. dose. At 6 h after each dose, active concentrations were still present in serum. The results suggest that cefodizime administered i.v. and i.m. has equivalent high cure rates in uncomplicated gonorrhea. This hypothesis should be tested further by a controlled clinical trial. If equivalent, i.v. administration excels because it is better tolerated locally.