Nothing
Kovalenko_2020_dupilumab <- function() {
description <- "Dupilumab PK model (Kovalenko 2020)"
reference <- "Kovalenko P, Davis JD, Li M, et al. Base and Covariate Population Pharmacokinetic Analyses of Dupilumab Using Phase 3 Data. Clinical Pharmacology in Drug Development. 2020;9(6):756-767. doi:10.1002/cpdd.780"
units<-list(time="day", dosing="mg")
# Model 1 from table 1 and supplementary Table 2 in the publication and its
# supplement.
covariateData <-
list(
WT = "Body weight in kg"
)
ini({
lvc <- log(2.48); label("central volume (L)")
lke <- log(0.0534); label("elimination rate (1/d)")
lkcp <- log(0.213); label("central-to-peripheral rate (1/d)")
Mpc <- 0.686; label("ratio of kcp and kpc (kpc is peripheral to central rate with units of 1/d)")
lka <- log(0.256); label("absorption rate (1/d)")
lMTT <- log(0.105); label("mean transit time (d)")
lVm <- log(1.07); label("maximum target-mediated rate of elimination (mg/L/d)")
Km <- fixed(0.01); label("Michaelis-Menten constant (mg/L)")
lfdepot <- log(0.643); label("Bioavailability (fraction)")
e_wt_vc <- 0.711; label("Exponent of weight on central volume (unitless)")
etalvc ~ 0.192
etalke ~ 0.285
etalka ~ 0.474
etalvm ~ 0.236
etamtt ~ 0.525 # etamtt is assumed to be on log-scale MTT to prevent negative values; this is a difference relative to Supplementary Table 2
CcpropSd <- 0.15; label("Proportional residual error (fraction)")
CcaddSd <- fixed(0.03); label("Additive residual error (mg/L)")
})
model({
# Weight normalization to 75 kg is assumed based on prior publication. It
# is not specified in the current publication:
# Kovalenko P, DiCioccio AT, Davis JD, et al. Exploratory Population PK
# Analysis of Dupilumab, a Fully Human Monoclonal Antibody Against
# IL-4Ralpha, in Atopic Dermatitis Patients and Normal Volunteers. CPT
# Pharmacometrics Syst Pharmacol. 2016;5(11):617-624. doi:10.1002/psp4.12136
vc <- exp(lvc + etalvc)*(WT/75)^e_wt_vc
ke <- exp(lke + etalke)
kcp <- exp(lkcp)
ka <- exp(lka + etalka)
MTT <- exp(lMTT + etamtt)
Vm <- exp(lVm + etalvm)
# Derived parameters
kpc <- kcp/Mpc
ktr <- (3 + 1)/MTT
d/dt(depot) <- -ktr*depot
d/dt(transit1) <- ktr*(depot - transit1)
d/dt(transit2) <- ktr*(transit1 - transit2)
d/dt(transit3) <- ktr*transit2 - ka*transit3
# Linear and Michaelis-Menten clearance
d/dt(central) <- ka*transit3 - ke*central - kcp*central + kpc*periph - central*(Vm/(Km + central/vc))
d/dt(periph) <- kcp*central - kpc*periph
f(depot) <- exp(lfdepot)
# No unit conversion is required to change mg/L (dosing amount/central
# volume unit) to mg/L (measurement unit)
Cc <- central/vc
Cc ~ add(CcaddSd) + prop(CcpropSd)
})
}
Any scripts or data that you put into this service are public.
Add the following code to your website.
For more information on customizing the embed code, read Embedding Snippets.