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)