tests/testthat/test-model-rate.R

In nlmixr2/rxode2: Facilities for Simulating from ODE-Based Models

rxTest({
  ms <- c("liblsoda", "lsoda", "dop853")

  for (m in ms) {
    # context(sprintf("Modeled rate (%s)", m))

    mod.rate <- rxode2({
      a <- 6
      b <- 0.6
      f <- 1
      ri <- 10
      li <- 0
      d / dt(intestine) <- -a * intestine
      f(intestine) <- f
      rate(intestine) <- ri
      alag(intestine) <- li
      d / dt(blood) <- a * intestine - b * blood
    })

    et <- et() %>%
      et(amt = 2 / 24, rate = -1, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))


    et2 <- et() %>%
      et(amt = 2 / 24, rate = 2, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    f1.a <- rxSolve(mod.rate, et, c(ri = 2, f = 1, li = 0), method = m)
    f1.b <- rxSolve(mod.rate, et2, c(ri = 0.1, f = 1, li = 0), method = m)

    test_that("rate=2, f=1, lag=0 makes sense for modeled rate", {
      expect_equal(seq(0, 10, by = 1 / 24), f1.a$time)
      expect_equal(seq(0, 10, by = 1 / 24), f1.b$time)
      expect_equal(as.data.frame(f1.a), as.data.frame(f1.b))
    })

    f1.a <- rxSolve(mod.rate, et, c(ri = 2, f = 1, li = 0.5), method = m)
    f1.b <- rxSolve(mod.rate, et2, c(ri = 0.1, f = 1, li = 0.5), method = m)

    test_that("rate=2, f=1, lag=0.5 makes sense for modeled rate", {
      expect_equal(seq(0, 10, by = 1 / 24), f1.a$time)
      expect_equal(seq(0, 10, by = 1 / 24), f1.b$time)
      expect_equal(as.data.frame(f1.a), as.data.frame(f1.b))
    })

    f1.a <- rxSolve(mod.rate, et, c(ri = 2, f = 2, li = 0.5), method = m)
    f1.b <- rxSolve(mod.rate, et2, c(ri = 0.1, f = 2, li = 0.5), method = m)

    test_that("rate=2, f=2, lag=0.5 makes sense for modeled rate & fixed rate", {
      expect_equal(seq(0, 10, by = 1 / 24), f1.a$time)
      expect_equal(seq(0, 10, by = 1 / 24), f1.b$time)
      expect_equal(as.data.frame(f1.a), as.data.frame(f1.b))
    })

    et <- et() %>%
      et(amt = 2 / 24, rate = -1) %>%
      et(amt = 0.2, time = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    et2 <- et() %>%
      et(amt = 2 / 24, rate = 2) %>%
      et(amt = 0.2, time = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    f.a <- rxSolve(mod.rate, et, c(ri = 2, f = 2, li = 0.3), method = m)
    f.b <- rxSolve(mod.rate, et2, c(ri = 1e-6, f = 2, li = 0.3), method = m)

    test_that("rate=2 makes sense for modeled rate", {
      expect_equal(seq(0, 10, by = 1 / 24), f.a$time)
      expect_equal(seq(0, 10, by = 1 / 24), f.b$time)
      expect_equal(as.data.frame(f.a), as.data.frame(f.b))
    })

    f.a <- rxSolve(mod.rate, et, c(ri = 0.125, f = 2, li = 0.3), method = m)

    et2 <- et() %>%
      et(amt = 2 / 24, rate = 0.125) %>%
      et(amt = 0.2, time = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    f.b <- rxSolve(mod.rate, et2, c(ri = 1e-6, f = 2, li = 0.3), method = m)

    test_that("rate=0.125, f=2, lag=0.3 with 2 doses makes sense for modeled rate", {
      expect_equal(seq(0, 10, by = 1 / 24), f.a$time)
      expect_equal(seq(0, 10, by = 1 / 24), f.b$time)
      expect_equal(round(as.data.frame(f.a), 4), round(as.data.frame(f.b), 4))
    })

    f.a <- rxSolve(mod.rate, et, c(ri = 0.05, f = 2, li = 0.3), method = m)

    et2 <- et() %>%
      et(amt = 2 / 24, rate = 0.05) %>%
      et(amt = 0.2, time = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    f.b <- rxSolve(mod.rate, et2, c(ri = 1, f = 2, li = 0.3), method = m)

    et3 <- et() %>%
      et(amt = 2 / 24 * 2, rate = 0.05) %>%
      et(amt = 0.2 * 2, time = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    f.c <- rxSolve(mod.rate, et3, c(ri = 1, f = 1, li = 0.3), method = m)

    test_that("rate=0.05, f=2, lag=0.3 makes sense for modeled rate", {
      expect_equal(seq(0, 10, by = 1 / 24), f.a$time)
      expect_equal(seq(0, 10, by = 1 / 24), f.b$time)
      expect_equal(as.data.frame(f.a), as.data.frame(f.b))
    })

    test_that("bad rates (zero/negative) throw errors", {
      expect_error(rxSolve(mod.rate, et, c(ri = -1, f = 1, li = 0.3), method = m))
      expect_error(rxSolve(mod.rate, et, c(ri = 0, f = 1, li = 0.3), method = m))
    })

    mod.dur <- rxode2({
      a <- 6
      b <- 0.6
      f <- 1
      di <- 3
      li <- 0
      d / dt(intestine) <- -a * intestine
      f(intestine) <- f
      dur(intestine) <- di
      alag(intestine) <- li
      d / dt(blood) <- a * intestine - b * blood
    })

    test_that("Error when rate is requested but not in table", {
      expect_error(rxSolve(mod.dur, et, c(ri = 1, f = 1, li = 0.3), method = m))
    })

    # context(sprintf("Modeled duration (%s)", m))

    ## Now model duration
    et <- et(amt = 2 / 24 * 2, rate = -2) %>%
      et(amt = 0.2 * 2, time = 2) %>%
      et(seq(0, 10, by = 1 / 24))

    test_that("Error is thrown without modeled duration", {
      expect_error({
        rxSolve(mod.rate, et, c(ri = 1, f = 1, li = 0.3), method = m)
      })
    })

    f.a <- rxSolve(mod.dur, et, c(di = 0.5, f = 1, li = 0.3), method = m)

    et2 <- et() %>%
      et(amt = 2 / 24 * 2, dur = 0.5) %>%
      et(amt = 0.2 * 2, time = 2) %>%
      et(seq(0, 10, by = 1 / 24))

    f.b <- rxSolve(mod.dur, et2, c(di = 10, f = 1, li = 0.3), method = m)

    test_that("Duration 0.5, F=1, li=0.3", {
      expect_equal(as.data.frame(f.a), as.data.frame(f.b))
    })

    et2 <- et() %>%
      et(amt = 2 / 24 * 2, dur = 0.5) %>%
      et(amt = 0.2 * 2, time = 2) %>%
      et(seq(0, 10, by = 1 / 24))

    f.a <- rxSolve(mod.dur, et, c(di = 0.5, f = 1, li = 0.3), method = m)

    f.b <- rxSolve(mod.dur, et2, c(di = 10, f = 1, li = 0.3), method = m)

    test_that("Duration 0.5, F=1, li=0.3", {
      expect_equal(as.data.frame(f.a), as.data.frame(f.b))
    })

    f.a <- rxSolve(mod.dur, et, c(di = 0.5, f = 2, li = 0.3), method = m)

    f.b <- rxSolve(mod.dur, et2, c(di = 10, f = 2, li = 0.3), method = m)

    test_that("Duration 0.5, F=1, li=0.3", {
      expect_equal(as.data.frame(f.a), as.data.frame(f.b))
    })
  }

  test_that("error when bioavaibility(state)+rate/dur, but maintain f(state); Issues RxODE#216 and RxODE#222", {
    mod.rate <- rxode2({
      a <- 6
      b <- 0.6
      f <- 1
      ri <- 10
      li <- 0
      d / dt(intestine) <- -a * intestine
      f(intestine) <- f
      rate(intestine) <- ri * intestine
      alag(intestine) <- li
      d / dt(blood) <- a * intestine - b * blood
    })

    et <- et() %>%
      et(amt = 2 / 24, rate = -1, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    expect_error(rxSolve(mod.rate, et))

    mod.rate <- rxode2({
      a <- 6
      b <- 0.6
      f <- 1
      ri <- 10
      li <- 0
      d / dt(intestine) <- -a * intestine
      f(intestine) <- f
      dur(intestine) <- ri * intestine
      alag(intestine) <- li
      d / dt(blood) <- a * intestine - b * blood
    })

    et <- et() %>%
      et(amt = 2 / 24, rate = -1, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    expect_error(rxSolve(mod.rate, et))

    mod.rate <- rxode2({
      a <- 6
      b <- 0.6
      f <- 1
      ri <- 10
      li <- 0
      d / dt(intestine) <- -a * intestine
      f(intestine) <- f * intestine
      rate(intestine) <- ri
      alag(intestine) <- li
      d / dt(blood) <- a * intestine - b * blood
    })

    et <- et() %>%
      et(amt = 2 / 24, rate = 1, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    expect_error(rxSolve(mod.rate, et))

    et <- et() %>%
      et(amt = 2 / 24, rate = -1, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    expect_error(rxSolve(mod.rate, et))

    mod.rate <- rxode2({
      a <- 6
      b <- 0.6
      f <- 1
      ri <- 10
      li <- 0
      d / dt(intestine) <- -a * intestine
      f(intestine) <- f * intestine
      dur(intestine) <- ri
      alag(intestine) <- li
      d / dt(blood) <- a * intestine - b * blood
    })

    et <- et() %>%
      et(amt = 2 / 24, rate = -2, 0, addl = 9, ii = 1) %>%
      et(seq(0, 10, by = 1 / 24))

    expect_error(rxSolve(mod.rate, et))
  })

  test_that("Test that state-based bio-availability's does work", {
    CLp <- 25
    CLh <- 1
    fuinc <- 1
    Nh <- 0.4
    Vh <- 3.9
    V1 <- 1800
    ke <- 0.02
    sample.int <- 24
    Sample.V <- 20
    Days <- 5
    ini <- c(A1 = 1000, A2 = 0, V.ms = 0)
    mod <- "
  d/dt(V.ms) = 0

  Vme = ke * time
  V1 = V1 - Vme - V.ms
  C1 = A1 / V1
  C2 = A2 / V2
  d/dt(A1) =  CLp * fuinc * (C2 - C1)
  f(A1)    = (V1 - Sample.V) / V1
  d/dt(A2) =  CLp * fuinc * (C1 - C2) - CLh * C2 * Nh
  d/dt(M) = CLh * C2 * Nh
"
    mod <- rxode2(model = mod)

    par <- c(
      CLp = CLp, CLh = CLh, fuinc = fuinc, Nh = Nh, V2 = Vh,
      V1 = V1 - Sample.V, Sample.V = Sample.V, ke = ke, Cp1 = 0
    )

    sim.ev <- et(seq(0, Days * 60 * 24, by = 1)) %>%
      et(cmt = "V.ms", evid = 4, amt = Sample.V, nbr = 5, ii = sample.int * 60) %>%
      et(cmt = "A1", time = 1440, evid = 6, amt = 1)

    expect_error(rxSolve(mod, par, sim.ev, inits = ini, addDosing = TRUE), NA)
  })
})