Population pharmacokinetics of vancomycin in hemodialysis patients

Abstract

Introduction: Vancomycin is a glycopeptide antibiotic, which is primarily effective against Gram-positive aerobic and most Gram-positive anaerobic bacteria. It is known that the pharmacokinetics of vancomycin are significantly altered in hemodialysis patients, which may result in reduced efficacy or increased toxicity of the drug. Objective: The objective of this paper was to investigate the influence of several potential factors on the elimination of vancomycin in hemodialysis patients. Method: A retrospective observational study of case series type was conducted. The study includes hospitalized patients with terminal chronic renal failure who are on intermittent hemodialysis at the University Clinical Center Kragujevac (UKC KG) and who developed an infection with Gram-positive bacteria. Development of a one-compartment population pharmacokinetic (PPK) model without absorption for vancomycin was performed using the NONMEM software package. Results: A total of 60 critically ill patients on hemodialysis were included in this study. Estimated vancomycin clearance and volume of distribution values in the base model were 1.16 L/h and 324 L, respectively. The full PPK model of vancomycin had 5 significant covariates: daily dose of vancomycin, weekly number of hemodialysis sessions, duration of each dialysis session, co-administration of levofloxacin, and co-administration of fluconazole. It was shown that only 1 out of 5 individual covariates from the full model met the necessary statistical requirements, and that was the daily dose of vancomycin. Conclusion: Vancomycin clearance in hemodialysis patients depends on various factors, including dialysis efficiency and patient characteristics. Clinicians must carefully monitor vancomycin levels in hemodialysis patients, adjusting doses as needed to ensure therapeutic efficacy while minimizing the risk of toxicity.