Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis

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Abstract
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).