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KMID : 0191120130280010048
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Journal of Korean Medical Science
2013 Volume.28 No. 1 p.48 ~ p.54
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Serum Cystatin C Is a Major Predictor of Vancomycin Clearance in a Population Pharmacokinetic Analysis of Patients with Normal Serum Creatinine Concentrations
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Chung Jae-Yong
Jin Sung-Joon
Yoon Ji-Hyun
Song Young-Goo
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Abstract
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We developed a population pharmacokinetic model of vancomycin by integrating the effects of cystatin C and other demographic factors in a large population of Korean patients with normal serum creatinine concentrations to elucidate the precise role of serum cystatin C concentrations in the prediction of vancomycin clearance. A population pharmacokinetic model of vancomycin was developed using NONMEM software from a total of 1,373 vancomycin concentration measurements in 678 patients whose serum creatinine concentrations were lower than 1.2 mg/dL. Covariate selection revealed that cystatin C was the most influential factor and had negative influence (-0.78) in the relationship. Total body weight, sex, age, and serum creatinine were also significantly correlated with the clearance. The estimated intersubject variabilities of clearance and volume of distribution were 24.7% and 25.1%, respectively. A 14-fold difference in predicted trough concentrations was observed according to only cystatin C concentrations in a population of simulated individuals with median demographic characteristics. The use of serum cystatin C as marker of vancomycin clearance for more accurate predictions of serum vancomycin concentrations could be useful, particularly among patients with normal serum creatinine concentrations.
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KEYWORD
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Vancomycin, Cystatin C, Pharmacokinetics, NONMEM, TDM
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