Pharmacokinetic studies in animals and humans of a new cephalosporin, the sodium salt of 7-cyanacetamidocephalosporanic acid.

The sodium salt of 7-cyanacetamidocephalosporanic acid (CAA) had a relatively short serum half-life in rabbits (21 min by intravenous and 30 min by intramuscular administration) and in humans (33 min by intravenous injection). The drug was not extensively bound (about 35%) to serum in either species. Even after large doses (500 mg/kg), CAA was not well absorbed from the gastrointestinal tract of rabbits. Urinary excretion of antibacterial activity was rapid after intravenous and intramuscular administration in rabbits and after intravenous administration in men. Expressed as unchanged CAA, antibacterial activity appeared in the urine to the extent of 84% for humans, 35% for rabbits and 32% for rats. Excretion proceeded partly by active renal tubular secretion in rabbits. In this latter species, low concentrations of the active drug were detected in cerebrospinal fluid and bile after an intravenous dose of 25 mg/kg. CAA was well tolerated after intravenous administration of a single dose in both rabbits and humans.