Ceftizoxime elimination kinetics in continuous ambulatory peritoneal dialysis

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Abstract
The kinetics of ceftizoxime, a .beta.-lactamase stable cephalosporin [antibiotic active agonist most Enterobacteriaceae, gram-positive cocci, Haemophilus influenzae, Bacteroides fragilis, Neisseria gonorrhoeae and some strains of Pseudomonas aeruginosa], were investigated in 8 subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 500-mg or 1-g dose was injected i.v., or a 500-mg dose was given i.p. in the CAPD fluid during a 6-h dwell time. The ceftizoxime (500 mg) serum kinetic parameters were as follows: peak concentrations, 21-46 mg/l; volume of distribution, 0.27 l/kg; elimination rate constant, 0.0784/h; plasma clearance, 1.66 l/kg per h; and t1/2 [half-life], 10.2 h. The t1/2 after 1 g was 12 h. Dialysate ceftizoxime concentrations rose rapidly between 0.25 and 2 h and slowly over the next 4 h, but only 4.04 .+-. 1.8 and 7.4 .+-. 2.9 mg ceftizoxime/h was eliminated by the peritoneal route over a 6-h dwell time after 500 mg or 1 gm i.v. This represents only 4-5% of the dose. After i.p. instillation, the antibiotic appeared in the serum within 15 min in all 4 subjects, and the peak serum concentrations ranged from 12-19.8 mg/l (mean .+-. SD = 16.4 .+-. 3.3) between 5 and 6 h. Approximately 78% of ceftizoxime was absorbed from the peritoneal dialysis fluid during a single 6-h dwell time. Rate constant for absorption, ka, was 0.3959/h and absorption t1/2 was 1.75 h (as calculated by the residual equation). Ceftizoxime apparently exchange characteristics through the peritoneal membrane. Instillation of ceftizoxime in CAPD fluid alone may permit rapid absorption to reach therapeutic serum concentrations.

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