Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis

The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis. Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX. Multiple blood and dialysate samples were collected during the 72-h period after drug administration. The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v. administration were 2.2 +/- 1.0 h (mean +/- standard deviation), 0.17 +/- 0.03 liters/kg, and 81.0 +/- 31.0 ml/min, respectively. No significant differences were observed in these parameters after i.p. administration. The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 +/- 0.43 and 2.84 +/- 0.70 ml/min, respectively, after i.v. administration. The bioavailability of CTX after i.p. instillation was 74.6 +/- 21.3%. Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i.p. dosing. Administration (i.v.) of 2 g every 12 h or i.p. instillation of 2 g every 24 h may be used for the treatment of i.p. infections with highly susceptible organisms (MIC less than 1.0 microgram/ml).