Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis. Clinical pharmacokinetic considerations

Continuous ambulatory peritoneal dialysis (CAPD) is an accepted alternative to haemodialysis in the treatment of end-stage renal failure. The frequently used intraperitoneal administration of antibiotics to treat peritonitis and the possible role of CAPD in the elimination of drugs has stimulated pharmacokinetic research in this field. The 2 principal results derived from these studies are: (1) the elimination capacity of CAPD for drugs given systemically or orally is very low, and (2) drugs administered intraperitoneally rapidly enter the circulation, a significant amount of drug being absorbed from the peritoneal cavity. This pharmacokinetic behavior is easily understood considering some basic and simple pharmacokinetic principles: the higher the volume of distribution of a substance, the lower will be the percentage of drug present in the peritoneal cavity. Thus, a prerequisite for rapid drug elimination by CAPD is a low body volume of distribution of a particular drug. Only in such a case will the drug diffuse into the peritoneal space to a significant extent. For dosing regimens in CAPD patients, the fraction of the dose eliminated by the peritoneal route should be known or estimated. This fraction depends on the relation of the peritoneal clearance to the total body clearance, and on the protein binding of the drug. The low flow rate of the peritoneal effluent (approximately 10 L/day = 7 ml/min) appears to be the most important limiting factor for the low extraction capacity of CAPD. The list of drugs that have been found to be significantly eliminated by CAPD is short: particular mention should be made of the aminoglycosides and some cephalosporins. The data on the peritoneal elimination of vancomycin are inconsistent. Although the intravenous and oral routes have been successfully used for the treatment of peritonitis, the time course of antibiotic concentrations in the peritoneal space appears to favour the peritoneal route of drug administration. During peritonitis, intraperitoneally administered drugs enter the circulation more rapidly and completely, due to the increased permeability of the peritoneal membrane. As long as the dialysate outflow rate and protein binding of the drug are not extensively altered by peritoneal inflammation, however, the extraction capacity of CAPD appears to remain low.