Population pharmacokinetic parameters of vancomycin in critically ill patients.
BACKGROUND
Intensive care unit patients are a highly heterogeneous population. Accurate dosing for this population requires characterization of the appropriate pharmacokinetic parameters.


OBJECTIVE
To estimate population pharmacokinetic parameters of vancomycin (VAN) in adult critically ill patients and to establish the predictive performance of the resulting model.


METHODS
Fifty critically ill patients with suspected or documented infection with VAN-sensitive micro-organisms were included. Thirty patients and 234 serum concentration-time sets obtained during clinical routine monitoring were used to estimate the pharmacokinetic parameters (group A). An open bicompartimental model with intermittent intravenous administration was used to adjust the data. Data were evaluated using a nonlinear mixed effects model (nonmem software). Forty plasma concentration-time data sets from 20 patients were used for validation using the Bayesian method (group B).


RESULTS
There was a linear relationship between creatinine clearance (Cl(cr)) and VAN clearance (Cl(VAN)). The inclusion of the non-renal clearance (Cl(nr)) (intercept of Cl(VAN) vs. Cl(cr) relationship) improved the model significantly (Cl(nr) 17 mL/min). The volume of distribution seems to be larger than previously reported: volume of the central compartment (V(c)) was 0.41 L/kg and volume of the peripheral compartment was (V(p)), 1.32 L/kg. The mean error (bias) and mean absolute error (precision) for predicting subsequent peak concentrations were -2.16 and 9.28 mg/L and for trough concentrations, -0.22 and 3.87 mg/L respectively.


CONCLUSIONS
The use of population-specific pharmacokinetic parameters and Bayesian forecasting improves dosage-regimen design.
Llopis-Salvia
P
P
Pharmacy Department, Hospital de la Ribera, Alzira, Valencia, Spain. pllopis@hosptial-ribera.com
Jiménez-Torres
N V
NV
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D003404:Creatinine / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008962:Models, Theoretical; D012189:Retrospective Studies; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine