Cefodizime, a new 2-aminothiazolyl cephalosporin: physicochemical properties, toxicology and structure-activity relationships.

Cefodizime is a 2-aminothiazolyl cephalosporin for parenteral use. Cefodizime has a bisubstituted thiothiazole moiety in position 3 of the cephem nucleus. The presence of this moiety does not alter the in-vitro antibacterial activity, or safety in animal studies, which are similar to those of cefotaxime, but results in an apparent long elimination half-life in rodents and dogs, and in novel immunological properties.

The pharmacokinetics of cefodizime following intravenous and intramuscular administration of a single dose of 1.0 g.

The pharmacokinetics and absolute bioavailability of cefodizime were determined after iv and im administration of a single 1.0 g dose in eight healthy volunteers. The absolute bioavailability of cefodizime after im injection of 1.0 g was 88% and 91% when determined by two different formulae.

Pharmacokinetics of cefodizime administered intravenously as a single-dose (1.0 and 2.0 g) to healthy adult volunteers.

Cefodizime is a new third generation cephalosporin for parenteral use. The purpose of this study was to define the pharmacokinetic profile of cefodizime after intravenous dosing with 1.0 and 2.0 g in healthy adult volunteers. Concentrations in plasma were determined over a period of 34 h and in urine over 48 h, using high-pressure liquid chromatographic procedures. Cefodizime displays a long elimination half-life (3.5-3.7 h). Mean total clearance was 2.63 +/- 0.19 l/h and mean renal clearance was 1.37 +/- 0.15 l/h. Areas under the curve were 422 +/- 43 mg.h/l and 757 +/- 39 mg.h/l for 1.0 and 2.0 g respectively. The apparent volumes of distribution were 12.8 +/- 1.81 and 14.3 +/- 1.11. After 1.0 g administration the residual concentrations were 3.94 +/- 0.79 mg/l and 0.38 +/- 0.10 mg/l at 12 and 24 h, respectively; after 2.0 g administration the residual concentrations were 6.80 +/- 1.40 mg/l and 0.65 +/- 0.18 mg/l, at 12 h and 24 h. Cefodizime is mainly eliminated via the kidneys. This profile supports once-daily administration of cefodizime, when indicated in non-life-threatening infections.

Pharmacokinetics of cefodizime in elderly patients with moderate or severe renal impairment.

In young adults, the elimination half-life of cefodizime is 3.5-4 h. A pharmacokinetic study was performed in eight patients, aged 63 to 85 years, divided into two groups with the following creatinine clearances (group I: greater than or equal to 50 ml/min and group II: less than 30 ml/min). Cefodizime was administered as a 1.0-g iv bolus. In group I, pharmacokinetic parameters did not differ from those observed in young healthy volunteers in a previous study. In group II, the half-life was increased (3.42-7.41 h). There is a linear correlation between the creatinine clearance and total clearance. The daily dose given needs to be based not on the age of the patient but on the degree of renal impairment. In elderly patients with severe renal impairment, the daily dose should be reduced if the creatinine clearance falls below 30 ml/min.