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dmta_ds <- lapply(1:8, function(i) {
ds_i <- dimethenamid_2018$ds[[i]]$data
ds_i[ds_i$name == "DMTAP", "name"] <- "DMTA"
ds_i$time <- ds_i$time * dimethenamid_2018$f_time_norm[i]
ds_i
})
names(dmta_ds) <- sapply(dimethenamid_2018$ds, function(ds) ds$title)
dmta_ds[["Borstel"]] <- rbind(dmta_ds[["Borstel 1"]], dmta_ds[["Borstel 2"]])
dmta_ds[["Borstel 1"]] <- NULL
dmta_ds[["Borstel 2"]] <- NULL
dmta_ds[["Elliot"]] <- rbind(dmta_ds[["Elliot 1"]], dmta_ds[["Elliot 2"]])
dmta_ds[["Elliot 1"]] <- NULL
dmta_ds[["Elliot 2"]] <- NULL
dfop_sfo3_plus <- mkinmod(
DMTA = mkinsub("DFOP", c("M23", "M27", "M31")),
M23 = mkinsub("SFO"),
M27 = mkinsub("SFO"),
M31 = mkinsub("SFO", "M27", sink = FALSE),
quiet = TRUE
)
f_dmta_mkin_tc <- mmkin(
list("DFOP-SFO3+" = dfop_sfo3_plus),
dmta_ds, quiet = TRUE, error_model = "tc")
d_dmta_nlmixr <- nlmixr_data(f_dmta_mkin_tc)
m_dmta_nlmixr <- function ()
{
ini({
DMTA_0 = 98.7697627680706
eta.DMTA_0 ~ 2.35171765917765
log_k_M23 = -3.92162409637283
eta.log_k_M23 ~ 0.549278519419884
log_k_M27 = -4.33774620773911
eta.log_k_M27 ~ 0.864474956685295
log_k_M31 = -4.24767627688461
eta.log_k_M31 ~ 0.750297149164171
f_DMTA_tffm0_1_qlogis = -2.092409
eta.f_DMTA_tffm0_1_qlogis ~ 0.3
f_DMTA_tffm0_2_qlogis = -2.180576
eta.f_DMTA_tffm0_2_qlogis ~ 0.3
f_DMTA_tffm0_3_qlogis = -2.142672
eta.f_DMTA_tffm0_3_qlogis ~ 0.3
log_k1 = -2.2341008812259
eta.log_k1 ~ 0.902976221565793
log_k2 = -3.7762779983269
eta.log_k2 ~ 1.57684519529298
g_qlogis = 0.450175725479389
eta.g_qlogis ~ 3.0851335687675
sigma_low_DMTA = 0.697933852349996
rsd_high_DMTA = 0.0257724286053519
sigma_low_M23 = 0.697933852349996
rsd_high_M23 = 0.0257724286053519
sigma_low_M27 = 0.697933852349996
rsd_high_M27 = 0.0257724286053519
sigma_low_M31 = 0.697933852349996
rsd_high_M31 = 0.0257724286053519
})
model({
DMTA_0_model = DMTA_0 + eta.DMTA_0
DMTA(0) = DMTA_0_model
k_M23 = exp(log_k_M23 + eta.log_k_M23)
k_M27 = exp(log_k_M27 + eta.log_k_M27)
k_M31 = exp(log_k_M31 + eta.log_k_M31)
k1 = exp(log_k1 + eta.log_k1)
k2 = exp(log_k2 + eta.log_k2)
g = expit(g_qlogis + eta.g_qlogis)
f_DMTA_tffm0_1 = expit(f_DMTA_tffm0_1_qlogis + eta.f_DMTA_tffm0_1_qlogis)
f_DMTA_tffm0_2 = expit(f_DMTA_tffm0_2_qlogis + eta.f_DMTA_tffm0_2_qlogis)
f_DMTA_tffm0_3 = expit(f_DMTA_tffm0_3_qlogis + eta.f_DMTA_tffm0_3_qlogis)
f_DMTA_to_M23 = f_DMTA_tffm0_1
f_DMTA_to_M27 = (1 - f_DMTA_tffm0_1) * f_DMTA_tffm0_2
f_DMTA_to_M31 = (1 - f_DMTA_tffm0_1) * (1 - f_DMTA_tffm0_2) * f_DMTA_tffm0_3
d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 -
g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 -
g) * exp(-k2 * time))) * DMTA
d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) +
k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
(1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23
d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) +
k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
(1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 +
k_M31 * M31
d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) +
k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
(1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31
DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA)
M23 ~ add(sigma_low_M23) + prop(rsd_high_M23)
M27 ~ add(sigma_low_M27) + prop(rsd_high_M27)
M31 ~ add(sigma_low_M31) + prop(rsd_high_M31)
})
}
m_dmta_nlmixr_mkin <- nlmixr_model(f_dmta_mkin_tc, test_log_parms = TRUE)
f_dmta_nlmixr_saem <- nlmixr(f_dmta_mkin_tc, est = "saem", control = saemControl(print = 250))
f_dmta_nlmixr_focei <- nlmixr(f_dmta_mkin_tc, est = "focei", control = foceiControl(print = 250))
plot(f_dmta_nlmixr_saem)
plot(f_dmta_nlmixr_focei)
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