Pharmacokinetic profile of cefodizime.

The pharmacokinetics of cefodizime (CDZ) were determined after i.v. and i.m. administration of single doses of up to 2 g and after i.v. administration of 2 g b.i.d. for six days. Serum concentrations were adequately described by three exponential functions, with a terminal half-life of about 4 h. Serum and urine levels and amounts excreted were dose-proportional, and derived pharmacokinetic characteristics were dose-independent. Steady state was established after the second dose (b.i.d.). CDZ is 100% bioavailable after i.m. administration. Concomitant administration of lidocaine did not alter either bioavailability or pharmacokinetic characteristics. Following administration of 1 and 2 g i.m., Cmax was reached after 1.2 h and amounted to 60 and 140 mg/l, respectively. CDZ is 88% bound to plasma proteins. CDZ was predominantly eliminated by the kidneys (80% of dose), a further 20% being excreted in the bile. Metabolites were not detectable in serum or urine. Dose adjustment does not seem warranted in the elderly. For renally impaired patients with CLcr between 30 and 10 ml/min, the daily dose should not exceed 2 g. For patients with CLcr below 10 ml/min, individual adjustment is suggested. CDZ showed good penetration into tissues and biological fluids (lung, bronchial secretions, pleural fluid, kidney, prostate, urine, bone, muscle, skin, Fallopian tube) with long-lasting concentrations. In urine, therapeutic concentrations were present for more than 24 h after administration of 1 and 2 g. Thus, on the basis of its pharmacokinetic profile, cefodizime is appropriate for effective treatment with once-daily administration.