title: Serum cystatin C is a major predictor of vancomycin clearance in a population pharmacokinetic analysis of patients with normal serum creatinine concentrations.
abstract: 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.
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea.
authors: Jae-Yong
authors: JY
authors: Chung
authors: Sung-Joon
authors: SJ
authors: Jin
authors: Ji-Hyun
authors: JH
authors: Yoon
authors: Young-Goo
authors: YG
authors: Song
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D003710:Demography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D012737:Sex Factors; D012984:Software; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D055316:Cystatin C; D014640:Vancomycin; D003404:Creatinine
keywords: Cystatin C; NONMEM; Pharmacokinetics; TDM; Vancomycin