Abstract: PO0997
Pharmacokinetics of Intraperitoneal Vancomycin in Patients on Automated Peritoneal Dialysis
Session Information
- Peritoneal Dialysis
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 702 Dialysis: Home Dialysis and Peritoneal Dialysis
Authors
- Lam, Edwin, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
- Kraft, Walter K., Thomas Jefferson University, Philadelphia, Pennsylvania, United States
- Stickle, Douglas F., Thomas Jefferson University, Philadelphia, Pennsylvania, United States
- Piraino, Beth M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Zhang, JingJing, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
Background
It is unclear if the pharmacokinetics of vancomycin is the same during automated peritoneal dialysis (APD) where cycler exchanges may affect the systemic, peritoneal, and urinary disposition of drug.
Methods
This was a prospective pharmacokinetic study in peritonitis-negative patients on APD. A single dose of vancomycin (20 mg/kg) was administered through the peritoneum and allowed to dwell for at least 15 hours. Patients underwent four drug-free exchanges following the initial dwell period. Plasma, dialysate and urine were collected over the course of 7 days for pharmacokinetic analysis. A non-compartmental analysis was used to estimate vancomycin pharmacokinetic parameters.
Results
Four patients enrolled and completed the study with no adverse events. Three patients had residual renal function. Following a median (range) dwell of 14.6 (14.2 – 17.6 hours), the mean (+ SD) observed maximum plasma concentration was 28.7 + 4.9 mg/L with a mean (+ SD) bioavailability of 98.5 + 1.4% prior to starting the cycler. The overall mean plasma clearance estimated from study start to completion was was 7.3 + 1.2 mL/min. In patients with residual renal function, the mean (+ SD) vancomycin renal clearance was 3.1 + 1.5 mL/min.
Conclusion
Despite the small sample size, this pilot study suggest that the dwell time has important implications for systemic vancomycin exposure, time to therapeutic plasma concentration, and dosing. Dose is driven by dwell time while 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.
Plasma, dialysis, and urine pharmacokinetic parameters following a single intraperitoneal dose.
Tmax (hours) | Cmax (mg/L) | AUC0-last (hr x mg/L) | CL/F (mL/min)§ | CLrenal (mL/min) | CLAPD (mL/min) | CL/F (mL/min)* | V/F (L) | Plasma t1/2 (hours) | Peritoneum-Plasma Transfer t1/2 (hours) | |
Subject 1 | 13.8 | 34.4 | 3089.0 | 7.4 | 1.6 | 7.1 | 11.6 | 62.7 | 98.2 | 2.9 |
Subject 2 | 14.9 | 25.5 | 2635.8 | 5.5 | - | 6.5 | 6.5 | 62.8 | 132.4 | 3.3 |
Subject 3 | 14.0 | 23.8 | 2292.9 | 7.3 | 2.5 | 14.6 | 17.0 | 63.8 | 100.4 | 3.3 |
Subject 4 | 15.0 | 31.2 | 2341.9 | 8.6 | 5.1 | 16.2 | 19.2 | 49.2 | 66.0 | 4.0 |
Mean | 14.4† | 28.7 | 2589.9 | 7.2 | 3.1 | 11.1 | 13.6 | 59.6 | 99.3† | 3.3† |
SD | 13.8 - 15.0‡ | 4.9 | 365.6 | 1.3 | 1.5 | 4.3 | 4.9 | 6.9 | 66.0 - 99.3‡ | 2.9 - 4.0‡ |
§Represents the total plasma clearance for the duration of the study. *Represents the total plasma clearance during the dialytic exchange period. †Median value reported. ‡Min and Max range reported.
Funding
- Other NIH Support