Liver Transplant Recipients Have Markedly Different Vancomycin Pharmacokinetics: A Pharmacokinetic Model-Based Analysis

Abstract

Background: Vancomycin is considered the antibiotic of choice for many gram-positive bacterial infections. Following the use of this medication, the risk of acute kidney injury (AKI) in patients increases significantly. Also, the kinetics of some medications, including vancomycin, differ between liver transplant recipients (LTRs) and the normal population.

Objective: The evaluation of the pharmacokinetics of vancomycin in LTRs and its association with the risk of AKI.

Methods: In this prospective study on 34 LTRs, blood samples were collected at specific time points from patients who had received vancomycin at 12-hour intervals, with a loading dose of 20–35 mg/kg and a maintenance dose of 15 20 mg/kg. The collected samples were analyzed using high-performance liquid chromatography (HPLC). Then, the area under the concentration-time curve (AUC) and other pharmacokinetic parameters were calculated. The occurrence of AKI and its related risk factors was also investigated.

Results: The mean observed values of Vd, Clvan, t₁/₂, and Ke for vancomycin were 1.08±0.66 L/kg, 4.91±2.98 L/h, 12.15±6.63 h, and 0.08±0.045 h⁻¹, respectively. All these pharmacokinetic parameters were significantly different in LTRs compared to the normal population. The incidence of AKI was 44.1%, which was higher than in healthy individuals. Factors that influenced the incidence of AKI included trough and intermediate concentrations, urinary tract infection (UTI), elimination constant (Ke), half-life (t₁/₂), AUC, length of hospital stay, serum albumin level, and baseline total and direct bilirubin concentrations.

Conclusion: Differences in pharmacokinetic parameters between LTRs and the general population underscore the need for vancomycin therapeutic drug monitoring (TDM) in all patients.