Pharmacokinetics of Cefazolin Compared with Four Other Cephalosporins

The pharmacokinetics of cefazolin were compared with those of cephaloridine, cephalothin, cephalexin, and cephanone in healthy adult male volunteers. The concentration of cefazolin in serum was twice as high after im and iv injections as that of cephaloridine, and four times as high as that of cephalothin. An iv infusion of 0.5 g of cefazolin during a period of 20 min gave a peak level in blood of 118 μg/ml, as compared with 70 μg/ml ml after a l-g dose of cephalothin. Higher levels in blood persisted for more than 8 hr with the former as compared with only about 2 hr with the latter. Half lives in serum were 1.8, 1.1, and 0.5 hr for cefazolin, cephaloridine, and cephalothin, respectively. Lower renal clearance of cefazolin (64 mllmin per 1.73 m2) as compared with values of 125 and 274 for cephaloridine and cephalothin, was the factor mainly responsible for its higher and more prolonged levels in blood. Renal clearance of cefazolin was essentially the same as its serum clearance, and almost 100% of the dose administered was recovered in the urine within 24 hr. Features that might offset, to some extent, these favorable characteristics of cefazolin are its high rate of binding to protein (86%) and its small apparent volume of distribution (10 liter/l.73 m2).