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The pharmacokinetics of the main metabolites of cefcanel daloxate hydrochloride, a new oral cephalosporin diester prodrug, was investigated. Cefcanel is antimicrobially active. After oral administration of a single dose of [14C]cefcanel daloxate hydrochloride to 7 healthy male volunteers (group A), plasma concentrations (t1/2 approximately 1 hr) and excretion of radioactivity, cefcanel (Aer = 38.2 +/- 3.8%, t1/2 approximately 1 hr), mandelic acid glycine conjugate (Aer = 3.7 +/- 0.5%, t1/2 approximately 15 hr) and N-mandelyl-2-aminoethanol (Aer = 7.5 +/- 3.0%) were evaluated. The absolute oral bioavailability of cefcanel was approximately 40% after administration of cefcanel daloxate hydrochloride and the extent of urinary excretion of cefcanel, mandelic acid glycine conjugate, and N-mandelyl-2-aminoethanol after an equimolar intravenous administration of cefcanel, were determined in a separate, similar group of volunteers (N = 12, group B). Total plasma clearance of cefcanel was 179.1 +/- 22.4 ml/min/1.73 m2 after intravenous administration. Renal clearances of cefcanel were 173.9 +/- 95.6 (po, group B), 166.6 +/- 31.9 (i.v., group B), and 136.3 +/- 16.1 ml/min/1.73 m2 (po, group A). Cefcanel was almost completely (92.6 +/- 7.3%) excreted in the urine as unmetabolized drug after intravenous administration (group B). However, when cefcanel daloxate hydrochloride was administered orally, more than 30% of the total urinary excretion was due to metabolites other than cefcanel. A large proportion of these metabolites were formed at a late stage, in the absence of systemic cefcanel. It is probable that biotransformed materials, distinct from cefcanel, were formed in the gastrointestinal tract and slowly absorbed rather than being systemic products of metabolic degradation of cefcanel.(ABSTRACT TRUNCATED AT 250 WORDS)