Pharmacokinetics of Intraperitoneal Cefotaxime in Children with Peritonitis Undergoing Continuous Ambulatory Peritoneal Dialysis

Abstract

Sir: Intraperitoneal therapy with cephalosporins is widely used for treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, pharmacokinetic data on peritoneal absorption of antibiotics in children are rare. We therefore studied the pharmacokinetics of intraperitoneal cefotaxime in 6 children (aged 1.1-14.8 years) undergoing CAPD for at least 2 months with acute peritonitis. One patient was studied twice with an interval of 2.3 years. Following the clinical diagnosis of acute peritonitis, cefotaxime in a concentration of 500 mg/L dialysate was applied in the peritoneal cavity for 6 h. Serum and dialysate concentrations of cefotaxime and its main metabolite desacetyl-cefotaxime were measured at multiple time points after extraction by high performance liquid chromatography in our laboratory; modified method of Dell et at. (1). Mean serum concentration of cefotaxime peaked at 40 min with 26.9 p 7.8 mg/L and thereafter decreased to 6.9 p 2.3 mg/L after 6 hrs (Figure 1). The peak concentration in our study was higher compared to data previously reported in adults without peritonitis using the same intraperitoneal doses of cefotaxime (2, 3). This can, at least in part, be explained by the fact that the doses administered are higher in children as in adults when corrected for body-weight (20.5 mg/kg compared to 14.3 mg/kg when calculated for an average adult weight of 70 kg). Installation of 1 g cefotax ime/L dialysate in adults without peritonitis resulted in serum concentration which are comparable to our values (4, 5). Mean peritoneal absorption of cefotaxime was 87% in our patients. This is in agreement with the results of Petersen et at. (6), who found an absorption of 90% in adults suffering from peritonitis. On the other hand, these values are higher than those abported in adults without peritonitis (56 78%, 2-6). We therefore assume that the peritoneal absorption is enhanced during peritonitis. Mean concentration of desacetyl-cefotaxime in serum rose within 3 hrs and then reached a plateau (Figure 1). The concentrations achieved correspond to the data reported in adults. In the dialysate, mean concentration of cefotaxime decreased continuously to 54.1 p 11.9 mg/L after 6 h dwell time (9% of the dose administered). Desacteylcefotaxime concentration in dialysate fell from 17.9 p 2.9 mg/L after 20 min to 12.9 p 2.5 mg/L after 6 h (Figure 2). Our results demonstrate that serum concentration of cefotaxime in antimicrobial levels (also against Staphylococcus species) is rapidly achieved after intraperitoneal administration of the drug (500 mg/L dialysate) in children with peritonitis and therapeutic levels will be maintained for several hours.