Impact of Hepatic Dysfunction on Vancomycin Area Under the Concentration–Time Curve Estimation and the Need for Early Therapeutic Drug Monitoring
Takaya Namiki, Yuki Hanai, Aiju Endo, Kazumi Hanawa, Hideki Hashi, Daiki Asakawa, Yoshiaki Yokoyama, Riku Maruyama, Shun Tsujimura, Yuki Igarashi, Yuki Enoki, Yurika Mizoguchi, Kazuaki MatsumotoBackground:
Renal function may be overestimated in patients with hepatic dysfunction because of reduced creatinine production; however, its impact on the vancomycin dosing regimen is unclear. In this study, the characteristics of steady-state vancomycin area under the concentration–time curve (AUC ss ) estimation and optimal strategies for its clinical management were determined.
Methods:
This multicenter, retrospective, observational study included adult patients who received vancomycin between January 2018 and December 2023; trough concentrations were measured. Patients with albumin levels of <2 g/dL with hepatic dysfunction were defined as having cirrhosis, hepatic failure, or other hepatic dysfunctions. A deviation of ≥30% in the AUC ss ratio, calculated as the Bayesian-estimated AUC using trough concentrations divided by the AUC derived from population pharmacokinetic parameters, was considered attributable to hepatic dysfunction. Multivariate analysis was conducted to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for factors associated with an AUC ss deviation of ≥30%.
Results:
In total, 157 patients (63 with and 94 without hepatic dysfunction) were included in the study. Multivariate analysis identified hepatic dysfunction (aOR, 2.257; 95% CI, 1.104–4.618) and creatinine clearance (aOR, 1.016; 95% CI, 1.006–1.027) as factors associated with an AUC
ss
deviation of ≥30%. Patients with hepatic dysfunction had higher AUC
ss
and steady-state trough ratios (
Conclusions:
Early therapeutic drug monitoring may be beneficial in patients with hepatic dysfunction because deviations of ≥30% between population-based and Bayesian AUC estimates have been observed in this population.