Cefuroxime: Human Pharmacokinetics

Abstract

Single doses of cefuroxime, a new parenteral cephalosporin, were given to 44 normal male subjects. Doses of 0.25, 0.5, 0.75, or 1.0 g were given intramuscularly to 33 volunteers. Mean peak serum concentrations of 14.8, 25.7, 34.6, and 40.0 μg/ml were assayed at 29 to 45 min, and measurable levels were present 8 h after the 0.5-g and higher doses. Single intravenous bolus doses of 0.25, 0.5, or 1.0 g were given to nine volunteers, and mean levels of 39, 66, and 99 μg/ml were assayed at 3 min. The antibiotic has a mean ultimate serum half-life of 70 min, a mean serum protein binding of 33%, a metabolic stability of greater than 95%, an apparent distribution volume of 11.1 to 15.8 liters/1.73 m ² depending on dose, and a mean urinary recovery of at least 95% for all parenteral doses. The cefuroxime/creatinine clearance ratios for all volunteers indicated that 43 to 54% of the antibiotic is secreted through the kidney tubules, and this was confirmed in some volunteers who received probenecid simultaneously. The injections by both routes were well tolerated, and the slight pain experienced after intramuscular injection disappeared within a few minutes. Physical and laboratory investigations in the volunteers showed that administration of cefuroxime had had no adverse effects. There was no evidence of absorption after oral administration.