Colin et al. 2019

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations

Clinical Pharmacokinetics · 10.1007/s40262-018-0727-5

Structure

A two-compartment model, driven by postmenstrual age, weight, serum creatinine and age.

Study population

General and Mixed patients — International, Europe, Asia and North America. Fitted to 2,544 patients and 8,300 concentration observations.

Equations

The model's structural parameters as Chorus implements them.

CL=5.312(V142.9)0.75FmatFmat,RFageFage,RFscrCL = 5.312 \cdot \left(\frac{V_1}{42.9}\right)^{0.75} \cdot \frac{F_{mat}}{F_{mat, R}} \cdot \frac{F_{age}}{F_{age, R}} \cdot F_{scr}Fmat=(PMA/52)2.88640.89322.8864+(PMA/52)2.8864F_{mat} = \frac{(PMA/52)^{2.8864}}{0.8932^{2.8864} + (PMA/52)^{2.8864}}Fage=(PMA/52)2.24161.5592.241+(PMA/52)2.241F_{age} = \frac{(PMA/52)^{-2.241}}{61.559^{-2.241} + (PMA/52)^{-2.241}}Fscr=exp(0.64856(SCrSCrstd))F_{scr} = \exp(-0.64856 \cdot (SCr - SCr_{std}))SCrstd=exp(1.22839+0.67190log10(PMA52)+6.27017exp(3.10940PMA52))SCr_{std} = \exp\left(-1.22839 + 0.67190 \cdot \log_{10}\left(\frac{PMA}{52}\right) + 6.27017 \cdot \exp\left(-3.10940 \cdot \frac{PMA}{52}\right)\right)PMAR=35+4052PMA_R = 35 + \frac{40}{52}V1=42.9Weight70V_1 = 42.9 \cdot \frac{Weight}{70}V2=41.68Weight70V_2 = 41.68 \cdot \frac{Weight}{70}Q=3.222(V241.68)0.75Q = 3.222 \cdot \left(\frac{V_2}{41.68}\right)^{0.75}
LaTeX source
CL = 5.312 \cdot \left(\frac{V_1}{42.9}\right)^{0.75} \cdot \frac{F_{mat}}{F_{mat, R}} \cdot \frac{F_{age}}{F_{age, R}} \cdot F_{scr}
F_{mat} = \frac{(PMA/52)^{2.8864}}{0.8932^{2.8864} + (PMA/52)^{2.8864}}
F_{age} = \frac{(PMA/52)^{-2.241}}{61.559^{-2.241} + (PMA/52)^{-2.241}}
F_{scr} = \exp(-0.64856 \cdot (SCr - SCr_{std}))
SCr_{std} = \exp\left(-1.22839 + 0.67190 \cdot \log_{10}\left(\frac{PMA}{52}\right) + 6.27017 \cdot \exp\left(-3.10940 \cdot \frac{PMA}{52}\right)\right)
PMA_R = 35 + \frac{40}{52}
V_1 = 42.9 \cdot \frac{Weight}{70}
V_2 = 41.68 \cdot \frac{Weight}{70}
Q = 3.222 \cdot \left(\frac{V_2}{41.68}\right)^{0.75}

Implementation notes

Pooled lifespan analysis (neonates to elderly). Features sigmoidal maturation/decline for clearance and age-dependent SCr reference.

Simulation settings

Models

selected

Dose candidates (mg)

Interval candidates (h)

Demographics

Physical characteristics.

kg
cm
yr