Intraperitoneal pharmacokinetics of vancomycin in patients on automated peritoneal dialysis

Abstract

It is unclear if the pharmacokinetics of vancomycin are the same during automated peritoneal dialysis (APD), where cycler exchanges may affect the systemic, peritoneal, and urinary disposition of drug. We conducted a prospective pharmacokinetic study evaluating the pharmacokinetics of vancomycin in plasma, dialysis fluid, and urine in peritonitis-negative patients on APD. Patients underwent four drug-free exchanges with 1.5% or 2.5% dextrose following the initial dwell period. Plasma, dialysis fluid, and urine was collected over the course of 7 days for pharmacokinetic analysis. Four patients completed the study with no adverse events. Following a median (range) dwell of 14.6 (14.2-17.6 h), the mean (±SD) observed maximum plasma concentration was 28.7 ± 4.9 mg/L with a mean bioavailability of 98.5 ± 1.4% prior to starting the cycler. The overall mean total plasma clearance estimated from study start to completion was 7.6 ± 1.2 ml/min. Mean total clearance during the dialytic exchange was 13.6 ± 4.9 ml/min. In patients with residual renal function, the mean vancomycin renal clearance was 3.1 ± 1.5 ml/min, representing 21.4%-58.9% of the overall total plasma clearance during the study period. Despite the small sample size, this pilot study suggests that the dwell time has important implications for systemic vancomycin exposure, time to therapeutic plasma concentration, and dosing. Dose is driven by dwell time, whereas the cycler determines the dosing interval. Rapid exchanges from APD will determine the frequency of dosing rather than the adequacy of absorption when vancomycin is given in the peritoneum.

Conflict of interest statement

The authors declared no competing interests for this work.

© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Figures

FIGURE 1

Study design and sampling schema

FIGURE 2

Bioavailability‐ represented as a percentage‐ over time during the drug‐dialysis fluid dwell

FIGURE 3

Individual plasma vancomycin concentration‐time profiles following a single 20 mg/kg intraperitoneal dose in 1‐liter of icodextrin

FIGURE 4

Vancomycin concentration in dialysis fluid during drug‐free dialysis fluid exchange. The initial end of dwell (i.e., EOD0) represents the concentration of drug‐dialysis fluid (icodextrin) whereas EOD1‐4 represents the concentrations after each drug‐free dwell and exchange. Subject 3 did not have detectable concentrations at EOD4. EOD, End of dwell

FIGURE 5

Individual dialysate vancomycin concentration‐time profiles following a single 20 mg/kg intraperitoneal dose in 1‐liter of icodextrin. The drug‐dialysis dwell period was expanded to show the decline in concentration during this period. The horizontal dash line represents the limit of quantification (2 mg/L)

FIGURE 6

Nonparametric superposition predictions for plasma concentration‐time profiles following five loading and maintenance dosing scenarios (vertical facet) and frequencies (horizontal facet). Predictions used single‐dose data established from the four patients in this study assuming complete drug absorption during the day dwell. The solid line represents mean concentrations (from the 4 patients) with the shaded regions representing the ±SD