Vancomycin Pharmacokinetics and Pharmacodynamics during Short Daily Hemodialysis

Background and objectives: Short daily hemodialysis (SDHD) is an alternative to thrice-weekly HD because of its putative physiologic benefits. The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics and pharmacodynamics of vancomycin. Design, setting, participants, & measurements: Six noninfected adults who had anuria and were treated with SDHD were studied and received four dialysis sessions over 4 days. After completion of the first SDHD, each patient received vancomycin 15 mg/kg by intravenous infusion. Blood samples were collected over the ensuing 3 days during each subsequent inter- and intradialytic period. Pharmacokinetic parameters were determined. Serum concentration-time profiles were simulated for four vancomycin regimens with maintenance doses administered after every other SDHD. Area under the serum-concentration time curve (AUC) from 0 to 48 hours, 48 to 96 hours, and 96 to 144 hours were calculated, and Monte Carlo simulations were performed to determine the probability of target attainment at an AUC/minimum inhibitory concentration (MIC) ratio >= 800 for each 48-hour AUC at MICs ranging from 0.5 to 2.0 mu g/ml. Results: Median (range) systemic clearance was 7.2 ml/min (5.3 to 10.0 ml/min), and dialytic clearance was 104 ml/min (94 to 106 ml/min). The steady-state volume of distribution was 55.4 L (34.8 to 77.2 L). At MICs <= 1 mu g/ml, probability of target attainment was >90% for each 48-hour AUC when vancomycin was administered as a 20-mg/kg loading dose followed by 10 mg/kg after every other SDHD. Conclusions: Vancomycin pharmacokinetic parameters in SDHD are consistent with data from thrice-weekly HD. A loading dose of 20 mg/kg followed by 10 mg/kg after every other SDHD provides adequate exposure for pathogens with MICs <= 1 mu g/ml. Clin J Am Soc Nephrol 5: 1981-1987, 2010. doi: 10.2215/CJN.03450410