Belabbas et al. 2023

Population pharmacokinetic model and dosing optimization of vancomycin in hematologic malignancies with neutropenia and augmented renal clearance

Journal of Infection and Chemotherapy · 10.1016/j.jiac.2023.01.010

Structure

A one-compartment model, driven by weight, creatinine clearance and neutropenia.

Study population

Hematologic malignancy and Neutropenia patients — Japan and Asia. Fitted to 148 patients and 681 concentration observations.

Covariate As reported
Age 59 (20–82) yr
Weight 57.9 (34.4–105) kg
BMI 21.4 (14.4–33.6) kg/m²
CrCl 112 (12.9–324) mL/min
SCr 0.58 (0.2–5.2) mg/dL

Reported as the source publication gives them — mean ± SD, or median with range or interquartile range.

Equations

The model's structural parameters as Chorus implements them.

CL=3.09(CrCl90)0.9731.07Neut(CrCl<130)CL = 3.09 \cdot \left(\frac{CrCl}{90}\right)^{0.973} \cdot 1.07^{Neut} \quad (CrCl < 130)CL=3.09(CrCl90)0.9731.13Neut(CrCl130)CL = 3.09 \cdot \left(\frac{CrCl}{90}\right)^{0.973} \cdot 1.13^{Neut} \quad (CrCl \geq 130)V1=122Weight70V_1 = 122 \cdot \frac{Weight}{70}
LaTeX source
CL = 3.09 \cdot \left(\frac{CrCl}{90}\right)^{0.973} \cdot 1.07^{Neut} \quad (CrCl < 130)
CL = 3.09 \cdot \left(\frac{CrCl}{90}\right)^{0.973} \cdot 1.13^{Neut} \quad (CrCl \geq 130)
V_1 = 122 \cdot \frac{Weight}{70}

Implementation notes

Final ARC-stratified model (eq. 2). Neutropenia multiplies clearance by 1.07 when CrCl < 130 mL/min and by 1.13 when CrCl ≥ 130 mL/min (the augmented-renal-clearance threshold), driven by the patient's neutropenia tag. The AML covariate (×1.15) is omitted: the calculator does not collect an AML-specific tag, and the broader hematologic-malignancy tag is intentionally not used for it to avoid over-applying the AML-specific clearance increase to non-AML patients.

Simulation settings

Models

selected

Dose candidates (mg)

Interval candidates (h)

Demographics

Physical characteristics.

kg
cm
yr