Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients

The pharmacokinetics of intravenous (i.v.) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single i.v. 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 (CI) 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 CI (CI(T)) was 7.4 +/- 2.0 mL/min. Renal CI (CI(R)) and PD CI (CI(PD)) accounted for 23.6% and 28.0% of CI(T). respectively. CI(R) correlated with GFR (CI(R) = 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 micro/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 i.p. thereafter (i.e., once daily) in APD patients.