Pharmacokinetics of Vancomycin in Healthy Korean Volunteers and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients with Normal Renal Function

Abstract

Background/Objectives: To date, population pharmacokinetic (PK) studies of vancomycin on healthy Korean adults have not been conducted. This study aimed to investigate the PK properties of vancomycin in healthy volunteers and to identify optimal dosing regimens based on the area under the concentration-time curve (AUC) in adult patients with normal renal function. Methods: We conducted a prospective clinical study, analysing PK samples from 12 healthy participants using noncompartmental analysis and non-linear mixed-effects modelling. The population PK parameters derived were employed in Monte Carlo simulations to evaluate the adequacy of the current dosing regimen and to formulate dosing recommendations. Results: The PK profiles were optimally described by a two-compartment model, with body weight and age as significant covariates affecting total clearance. The simulations indicated that to achieve a therapeutic target-defined as an AUC at steady-state over 24 h of 400-600 mg·h/L-daily doses ranging from 60 to 70 mg/kg are necessary in adults with normal renal function. Conclusions: This study underscores the need to actively adjust dosage and administration based on a vancomycin PK model that adequately reflects the demographic characteristics of patients to meet both safety and efficacy standards.

Keywords: Monte Carlo simulation; adult; healthy; normal renal function; population pharmacokinetics; vancomycin.

Figure 1

Goodness-of-fit plots for the final pharmacokinetic model of vancomycin: (a) conditional weighted residuals (CWRES) vs. time; (b) CWRES vs. population predicted concentration (PRED); (c) observed concentration vs. PRED; (d) observed concentration vs. individual predicted concentration (IPRED). The dashed lines represent smooth curves.

Figure 2

Probability of target attainment (PTA) for the intermittent infusion of vancomycin was assessed across six age groups (from 20–24 to 45–49 years) and administered at five dosage levels (10–30 mg/kg) over three dosing intervals (6, 8, and 12 h). Dots and lines represent therapeutic PTAs achieving an area under curve (AUC) ≥ 400 mg·h/L. The top of the figure represents the proportion of patients with AUC >600 among those achieving AUC ≥ 400. From top to bottom, these correspond to dosages of 30, 25, 20, 15, and 10 mg/kg.

Figure 3

Probability of target attainment (PTA) for continuous vancomycin infusions, as assessed across six age groups (from 20–24 to 45–49 years) at daily doses from 30 to 70 mg/kg. Dots and lines represent therapeutic PTAs achieving an AUC ≥ 400 mg·h/L. The top of the figure represents the proportion of patients with AUC > 600 among those achieving AUC ≥ 400. From top to bottom, these correspond to dosages of 30, 25, 20, 15, and 10 mg/kg.

Figure 4

Relationship between the area under the curve (AUC) and trough concentration for intermittent infusions of vancomycin evaluated across six age groups (from 20–24 to 45–49 years) and administered at five dosage levels (10–30 mg/kg) over three dosing intervals (6, 8, and 12 h). Squares indicate 400 mg·h/L ≤ AUC ≤ 600 mg·h/L and 15 mg/L ≤ trough concentration ≤ 20 mg/L. The top of the figure displays the correlation coefficient (R), p-value, and the linear regression equation.