title: Comparative pharmacokinetics of cefamandole, cephapirin, and cephalothin in healthy subjects and effect of repeated dosing.
abstract: Cefamandole nafate, cephapirin, and cephalothin were administered intravenously in crossover fashion to 12 volunteers, in dosages of 2 g every 6 h for 16 doses. Mean peak levels of cefamandole were approximately 50% higher than those of the other agents. The serum concentration curves appeared to decline bi-exponentially, suggesting that a two-compartment model was most applicable for pharmacokinetic analysis; accordingly, the t((1/2)) of cefamandole was significantly longer when the serum peak was omitted from the analysis (0.86 versus 0.73 h, P < 0.05). The half-lives of cephalothin and cephapirin, 0.34 and 0.36 h, respectively, were probably underestimates reflecting the inclusion of distribution-phase values in the calculation. Repeated dosing had no effect on the peak serum levels, half-life, serum clearance, or apparent volume of distribution with one exception: peak serum levels of cephapirin were significantly lower after the sixteenth than after the first dose. Marked variations within a given subject were noted in the half-life and apparent volume of distribution of cefamandole in several instances. Renal clearances of cefamandole exhibited saturation kinetics similar to those of penicillin G.
mesh_terms: D002511:Cephalosporins / Q000008:administration & dosage / Q000378:metabolism*; D002512:Cephalothin / Q000008:administration & dosage / Q000378:metabolism*; D002514:Cephapirin / Q000008:administration & dosage / Q000378:metabolism*; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008333:Mandelic Acids / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D002511:Cephalosporins; D008333:Mandelic Acids; D002514:Cephapirin; D002512:Cephalothin