Pharmacokinetics of intravenous and intraperitoneal cefotaxime in chronic ambulatory peritoneal dialysis

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Abstract
We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotoxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 .+-. 0.20 hours; volume of distribution, 0.35 .+-. 0.04 L/kg; total plasma clearance, 118.7 .+-. 12.3 ml/min; and peritoneal clearance, 6.7 .+-. 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 .mu.g/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% .+-. 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.

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