Decreased vancomycin clearance in patients with congestive heart failure.
OBJECTIVE
Congestive heart failure (CHF) alters the pharmacokinetics of various drugs, including cardiovascular agents, due to decreased cardiac output and decreased renal blood flow. The purpose of this study was to evaluate the influence of CHF on the clearance of vancomycin, a glycopeptide antibacterial agent.


METHODS
After reviewing more than 1,500 clinical charts of patients who received vancomycin therapy and whose serum vancomycin level was monitored, we identified 101 patients who also had the left ventricular ejection fraction (LVEF) assessed at that time. The fluorescence polarization immunoassay method was used to measure vancomycin serum concentrations in these patients 1 h after the end of vancomycin infusion and just before the next administration. Using these two measurements, we calculated the pharmacokinetic parameters using the Bayesian estimator.


RESULTS
Patients with an LVEF of <40 % (16 patients) or those with an LVEF of ≥ 40 %  and <60 % (40 % ≤ LVEF < 60 % ; 32 patients) had a significantly lower vancomycin clearance than patients with LVEF of ≥ 60 % (53 patients) (2.29 ± 0.95 or 2.79 ± 0.99 vs. 3.50 ± 1.04 L/h; p < 0.001 or p < 0.01, respectively). Vancomycin clearance was strongly correlated not only with estimated creatinine clearance (CLcr) in patients with an LVEF of <40 % (r = 0.828) and 40 % ≤ LVEF < 60 % (r = 0.773), but also with an LVEF in patients with a CLcr of <60 mL/min (r = 0.646). Consistent with these findings, multiple regression analysis revealed that CLcr, LVEF and body weight were important independent variables for vancomycin clearance (r(2) = 0.649).


CONCLUSIONS
Vancomycin clearance decreased with decreasing cardiac function (LVEF) and decreasing CLcr. This finding suggests that vancomycin clearance is affected by cardiac function and would be predicted not only CLcr but also by LVEF.
Department of Pharmacy, National Hospital Organization-Osaka National Hospital, Osaka, Japan. shimamoto.yuko.hp@mail.ncvc.go.jp
Yuko
Y
Shimamoto
Tsuyoshi
T
Fukuda
Shinjiro
S
Tominari
Kyoko
K
Fukumoto
Kazuyuki
K
Ueno
Min
M
Dong
Kazuhiko
K
Tanaka
Takuma
T
Shirasaka
Katsuya
K
Komori
D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D003404:Creatinine / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D016231:Fluorescence Polarization Immunoassay; D005919:Glomerular Filtration Rate; D006207:Half-Life; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000503:physiopathology; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D012189:Retrospective Studies; D013318:Stroke Volume; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016277:Ventricular Function, Left
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine