Drug Therapy in Patients Undergoing Peritoneal Dialysis Clinical Pharmacokinetic Considerations

Abstract

Peritoneal dialysis has become an accepted treatment modality for end-stage renal disease. The introduction of continuous ambulatory peritoneal dialysis (CAPD) has further popularised this technique. The need for adjustment of drug dosage in patients with endstage renal disease and the need for supplemental dosages following haemodialysis are well recognised. Little documentation exists concerning the need for supplemental drug dosage in patients on peritoneal dialysis. Knowledge of the influence of peritoneal dialysis on the elimination of specific drugs is essential to the rational design of dosage regimens in patients undergoing this dialysis technique. This review addresses the clinical pharmacokinetic aspects of drug therapy in patients undergoing peritoneal dialysis and considers: the efficiency of the peritoneal membrane as a dialysing membrane; the effects of peritoneal dialysis on the pharmacokinetics of drugs; the pharmacokinetic models and estimation methods for peritoneal dialysis clearance and the effects of peritoneal dialysis on drug elimination; the influence of the pharmacokinetic parameters of drugs on drug dialysability; and the application of pharmacokinetic principles to the adjustment of drug dosage regimens in peritoneal dialysis patients. Data on drugs which have been studied in peritoneal dialysis are tabulated with inclusion of pharmacokinetic and dialysability information.

An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis

“…drug exposure (Table 3). These results are in good agreement with data for other antibiotics, such as fosfomycin, cefotaxime, teicoplanin, vancomycin, and aminoglycosides (3,12,13).…”

Teicoplanin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis after intravenous and intraperitoneal dosing

“…These values contrast sharply with mean elimination half-life values of 44 to 61 h noted in healthy volunteers with normal renal function (4,26,30). Similarly, the mean CL of 0.040 and 0.036 m/min per kg noted in this study and that of Brouard et al (3), respectively, were approximately 50% lower than values of 0.088 to 0.099 ml/min per kg noted in previous studies in patients with end-stage renal disease (1,27) and contrasted sharply with values of 0.198 to 0.265 ml/min per kg in healthy volunteers with normal renal (13,18).…”

Pharmacokinetics of single-dose intravenous, oral, and intraperitoneal pefloxacin in patients on chronic ambulatory peritoneal dialysis

“…Six hours after administration, pefloxacin concentrations in peritoneal fluid reached 90% of the plasma value of the intravenous group, but only 43% of that of the oral group, in relation to the delay of absorption, and this should be kept in mind in establishing guidelines for peritonitis therapy. Mean overall dialysis fluid/plasma concentration ratios in groups A and B above 0.80 reflect high diffusion from blood to the peritoneal cavity as expected on the basis of physicochemical properties of the drug, i.e., relatively low molecular weight (319), low protein binding (25%), liposolubility, and high volume of distribution (8,16). Total plasma clearance is affected very little by CAPD in relation to the small volume of exchange during each cycle.…”