Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients

The pharmacokinetics of intravenous (IV) vancomycin was studied in automate d peritoneal dialysis (APD) patients who received a single IV dose of vanco mycin (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 colle cted 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 parame ters were calculated assuming a one-compartment model. Glomerular filtratio n rate (GFR) and vancomycin clearance (CI) values were normalized to 1.73 m (2). 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 hour s off cycler. Vancomycin half-life was significantly different on-cycler th an off-cycler (11.6 +/- 5.2 hr vs 62.8 +/- 33.0 hr; p < 0.001). Vancomycin total Cl (CIT) was 7.4 t 2.0 mL/min. Renal Cl (CIR) and PD Cl (CIPD) accoun ted for 23.6% and 28.0% of CIT, respectively. CIR correlated with GFR (CIR = 0.90 GFR - 1.01; r(2) = 0.79; p = 0.008). Mean vancomycin serum and dialy sate end-of-dwell concentrations were above minimum inhibitory concentratio n of susceptible organisms (5 mug/mL) for the first cycler and the second a mbulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vanco mycin 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.