Hughes et al. 2024

Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity

Therapeutic Drug Monitoring · 10.1097/FTD.0000000000001214

Structure

A two-compartment model, driven by fat-free mass and creatinine clearance.

Study population

Obese patients — United States and North America. Fitted to 83 patients and 272 concentration observations.

Covariate As reported
Age 56.3 (24.3–89.3) yr
Weight 134 (91.6–218) kg
BMI 46.3 (40–70.3) kg/m²
CrCl 174.1 (30.2–579) mL/min
SCr 0.84 (0.4–2.51) 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=5.06(CrClFFM100)0.851CL = 5.06 \cdot \left(\frac{CrCl_{FFM}}{100}\right)^{0.851}V1=64.34FFM70V_1 = 64.34 \cdot \frac{FFM}{70}V2=59.0FFM70V_2 = 59.0 \cdot \frac{FFM}{70}Q=6.24Q = 6.24
LaTeX source
CL = 5.06 \cdot \left(\frac{CrCl_{FFM}}{100}\right)^{0.851}
V_1 = 64.34 \cdot \frac{FFM}{70}
V_2 = 59.0 \cdot \frac{FFM}{70}
Q = 6.24

Implementation notes

Model specifically developed for class 3 obesity (BMI ≥40 kg/m²). Parameters updated to utilize the NONMEM SAEM estimates rather than nlmixr2. Uses FFM (Janmahasatian) as input to Cockcroft-Gault for CrCl calculation.

Simulation settings

Models

selected

Dose candidates (mg)

Interval candidates (h)

Demographics

Physical characteristics.

kg
cm
yr