Intravenous Vancomycin Pharmacokinetics in Automated Peritoneal Dialysis Patients

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Abstract
The pharmacokinetics of intravenous (IV) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single IV dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (Cl) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 ± 9.9 years of age (mean ± SD)] who had received PD for a median 3.5 months (range 2 – 66 months) were studied. Dwell times were 2.3 ± 0.1 hours on cycler and 7.3 ± 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 ± 5.2 hr vs 62.8 ± 33.0 hr; p < 0.001). Vancomycin total Cl (ClT) was 7.4 ± 2.0 mL/min. Renal Cl (ClR) and PD Cl (ClPD) accounted for 23.6% and 28.0% of ClT, respectively. ClR correlated with GFR (ClR = 0.90 GFR – 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 mg/mL) for the first cycler and the second ambulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg IP thereafter ( i.e., once daily) in APD patients.