Vancomycin pharmacokinetics and pharmacodynamics during short daily hemodialysis.
OBJECTIVE
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.


METHODS
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 μg/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 μg/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 μg/ml.
Decker
Brian S
BS
Indiana University School of Medicine, Indianapolis, IN, USA. bsdecker@iupui.edu
Kays
Michael B
MB
Chambers
Mary
M
Kraus
Michael A
MA
Moe
Sharon M
SM
Sowinski
Kevin M
KM
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001002:Anuria / Q000097:blood / Q000628:therapy*; D019540:Area Under Curve; D003198:Computer Simulation; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007196:Indiana; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D006435:Renal Dialysis / Q000379:methods*; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D014640:Vancomycin