Drug Dosing Consideration in Patients With Acute and Chronic Kidney Disease

A Clinical Update From Kidney Disease: Improving Global Outcomes (KDIGO)

Gary R Matzke; George R Aronoff; Arthur J Atkinson Jr; William M Bennett; Brian S Decker; Kai-Uwe Eckardt; Thomas Golper; Darren W Grabe; Bertram Kasiske; Frieder Keller; Jan T Kielstein; Ravindra Mehta; Bruce A Mueller; Deborah A Pasko; Franz Schaefer; Domenic A Sica; Lesley A Inker; Jason G Umans; Patrick Murray


Kidney Int. 2011;80(11):1122-1137. 

In This Article

Drug Dosing Considerations for Patients Receiving Peritoneal Dialysis

Peritoneal dialysis as practiced in 2011 is very unlikely to enhance total body clearance of any drug by more than 10 ml/min, as most typical peritoneal dialysis prescriptions are designed to achieve a urea clearance of ~10 ml/min. As most drugs are larger than urea, their clearance is even less; thus, drug clearance will likely be in the range of 5 to 7.5 ml/min. Many studies performed in the 1970s and 1980s showed that drug clearances by peritoneal dialysis were in this range, and thus one can conclude that peritoneal dialysis does not enhance drug removal to a degree that will require a dosage regimen modification.[151–154] Therefore, drug therapy recommendations for those with CLcr or eGFR <15 ml/min are likely clinically useful.

PK and PD Data

In patients with established peritoneal dialysis, the access to the peritoneal cavity provides an opportunity to deliver drugs both locally and systemically. The degree and rate of drug transport across the peritoneum depends on the dialysate volume in which the drug is diluted, the dialysate to plasma concentration gradient, the molecular size and electrochemical properties of the drug, the exposure time, and the peritoneal perfusion rate.[155] Intraperitoneal drug administration is well accepted for the treatment of peritoneal dialysis-associated peritonitis and other infections.[156,157] Intraperitoneal therapy appears attractive but has several potential technical pitfalls: solubility and stability of the compounds in peritoneal dialysis fluid,[158,159] and co-administration of more than one compound can lead to chemical interactions and changes in solubility. Administration intervals depend on the half-life of the drug, which is mainly determined by residual renal and extrarenal metabolic clearance. Long-standing experience with intermittent antibiotic administration exists for the glycopeptides vancomycin and teicoplanin, which can be administered at 5- to 7-day intervals, as well as for aminoglycosides and cephalosporins, which are suitable for once-daily dosing.[156,160,161]

Drug Dosing Approaches

Although the concept of intermittent antibiotic administration appears intriguing because of its practicality and cost efficiency, the efficacy and safety of intermittent dosing is impacted by several factors. Most importantly, the dialysate flow rate strongly affects the elimination of the drug.[161] In patients treated by automated peritoneal dialysis with frequent short dialysis cycles, exposure to peritoneal dialysis fluid with a given antibiotic concentration over several cycles may result in higher plasma concentrations as compared with antibiotic loading in a single extended dwell period in patients on continuous ambulatory peritoneal dialysis. Conversely, the higher dialysate flow and small molecule clearance achieved with automated peritoneal dialysis regimens may lead to a greater peritoneal clearance of antibiotic in the periods between dosing (Table 8).[157]


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