Pharmacokinetics of cefodizime: a review of the data on file

Abstract

Cefodizime is a new aminothiazolyl cephalosporin which may be administered iv or im. The absolute bioavailability im is almost 100%. The mean volume of distribution is approximately 6.2-8.51. Protein binding of cefodizime is 73-89% over the plasma concentration range. Cefodizime penetrates into several tissues and body fluids such as lung, sputum, pleural and ascitic fluids, prostate, kidney, and urine to give concentrations often exceeding the MICs of susceptible pathogens. Total body clearance is low (35-52 ml/min) and clearance is predominantly renal with up to 80% of an iv dose recovered unchanged in the urine. The pharmacokinetics are linear within the range of doses studied (0.5-2 g). The plasma concentration profile is best described by a triple exponential function. The ranges of half-lives reported are as follows: the distribution half-life is 0.2-0.5 h (accounting for 6-15% of the AUC), the beta half-life is 1.5-2.1 h (accounting for 56-76% of the AUC), and the terminal (gamma) half-life is 3.9-7.9 h (accounting for 18-43% of the AUC) After 2 g bd for five days in healthy volunteers, steady state was reached on the second administration, and no accumulation of the drug was noted. The total clearance is about 20% less in elderly subjects than in young adults, but no dosing adjustment is needed in the elderly. The pharmacokinetic profile is significantly altered in patients with a creatinine clearance less than 30 ml/min (three- to five-fold increase in half-life). Accordingly, the dose should be reduced to 50% of normal, at the same dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)