Systemic absorption of intraperitoneal antimicrobials in continuous ambulatory peritoneal dialysis.
The factors that influence drug movement across the peritoneum are presented, and the feasibility of administering antimicrobials intraperitoneally to treat systemic infections in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is explored. Antimicrobials are often administered intraperitoneally to treat peritonitis in patients undergoing CAPD. It would be advantageous to administer antimicrobials by the same route to treat systemic infections as well. Factors that determine the propensity of a drug to cross the peritoneal membrane include molecular weight, protein binding, volume of distribution, ionic charge, water or lipid solubility, the permeability and surface area of the peritoneum, blood flow rate, dialysate dwell time, and the concentration of dextrose in the dialysate. The bioavailability of i.p. drugs has been determined (1) by measuring the area under the plasma concentration-time curve (AUC) of an i.p. dose and comparing it with the AUC of the same dose given i.v. and (2) by estimating the residual drug content in the dialysate after a specified dwell period. Pharmacokinetic studies show that the bioavailabilities of antimicrobials given intraperitoneally in patients undergoing CAPD range from 50% to 92%. Vancomycin has been the agent most widely studied. Serum antimicrobial concentrations achieved by this route of administration are in many cases similar to those accomplished by the i.v. route and within the therapeutic range. Dosage regimens based on the pharmacokinetic data have been suggested; however, their efficacy has not been formally documented. The intraperitoneal route may have a role in the treatment of systemic infections in peritoneal dialysis patients, but specific recommendations cannot be made until clinical studies have been performed.
O'Brien
M A
MA
College of Pharmacy, University of Southern California, Los Angeles 90033.
Mason
N A
NA
D000042:Absorption; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002511:Cephalosporins / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D006801:Humans; D007274:Injections, Intraperitoneal; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum; D014640:Vancomycin / Q000493:pharmacokinetics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D014640:Vancomycin