Interpolate concentrations between measurements or extrapolate concentrations after the last measurement.

interpolate.conc() and extrapolate.conc() returns an interpolated (or extrapolated) concentration. interp.extrap.conc() will choose whether interpolation or extrapolation is required and will also operate on many concentrations. These will typically be used to estimate the concentration between two measured concentrations or after the last measured concentration. Of note, these functions will not extrapolate prior to the first point.

Usage

interp.extrap.conc(
  conc,
  time,
  time.out,
  lambda.z = NA,
  clast = pk.calc.clast.obs(conc, time),
  options = list(),
  method = NULL,
  auc.type = "AUCinf",
  interp.method,
  extrap.method,
  ...,
  conc.blq = NULL,
  conc.na = NULL,
  check = TRUE
)

interpolate.conc(
  conc,
  time,
  time.out,
  options = list(),
  method = NULL,
  interp.method,
  conc.blq = NULL,
  conc.na = NULL,
  conc.origin = 0,
  ...,
  check = TRUE
)

extrapolate.conc(
  conc,
  time,
  time.out,
  lambda.z = NA,
  clast = pk.calc.clast.obs(conc, time),
  auc.type = "AUCinf",
  extrap.method,
  options = list(),
  conc.na = NULL,
  conc.blq = NULL,
  ...,
  check = TRUE
)

interp.extrap.conc.dose(
  conc,
  time,
  time.dose,
  route.dose = "extravascular",
  duration.dose = NA,
  time.out,
  out.after = FALSE,
  options = list(),
  conc.blq = NULL,
  conc.na = NULL,
  ...,
  check = TRUE
)

Arguments

conc: Measured concentrations
time: Time of the measurement of the concentrations
time.out: Time when interpolation is requested (vector for interp.extrap.conc(), scalar otherwise)
lambda.z: The elimination rate (in units of inverse time) for extrapolation
clast: The last observed concentration above the limit of quantification. If not given, clast is calculated from pk.calc.clast.obs()
options: List of changes to the default PKNCA options (see PKNCA.options())
method: The method for integration (one of 'lin up/log down', 'lin-log', or 'linear')
auc.type: The type of AUC to compute. Choices are 'AUCinf', 'AUClast', and 'AUCall'.
interp.method, extrap.method: deprecated in favor of method and auc.type
...: Additional arguments passed to interpolate.conc() or extrapolate.conc().
conc.blq: How to handle BLQ values. (See clean.conc.blq() for usage instructions.)
conc.na: How to handle NA concentrations. (See clean.conc.na())
check: Run assert_conc_time(), clean.conc.blq(), and clean.conc.na()?
conc.origin: The concentration before the first measurement. conc.origin is typically used to set predose values to zero (default), set a predose concentration for endogenous compounds, or set predose concentrations to NA if otherwise unknown.
time.dose: Time of the dose
route.dose: What is the route of administration ("intravascular" or "extravascular"). See the details for how this parameter is used.
duration.dose: What is the duration of administration? See the details for how this parameter is used.
out.after: Should interpolation occur from the data before (FALSE) or after (TRUE) the interpolated point? See the details for how this parameter is used. It only has a meaningful effect at the instant of an IV bolus dose.

Value

The interpolated or extrapolated concentration value as a scalar double (or vector for interp.extrap.conc()).

Details

An NA value for the lambda.z parameter will prevent extrapolation.

extrap.method

'AUCinf': Use lambda.z to extrapolate beyond the last point with the half-life.
'AUCall': If the last point is above the limit of quantification or missing, this is identical to 'AUCinf'. If the last point is below the limit of quantification, then linear interpolation between the Clast and the next BLQ is used for that interval and all additional points are extrapolated as 0.
'AUClast': Extrapolates all points after the last above the limit of quantification as 0.

duration.dose and direction.out are ignored if route.dose == "extravascular". direction.out is ignored if duration.dose > 0.

route.dose and duration.dose affect how interpolation/extrapolation of the concentration occurs at the time of dosing. If route.dose == "intravascular" and duration.dose == 0 then extrapolation occurs for an IV bolus using pk.calc.c0() with the data after dosing. Otherwise (either route.dose == "extravascular" or duration.dose > 0), extrapolation occurs using the concentrations before dosing and estimating the half-life (or more precisely, estimating lambda.z). Finally, direction.out can change the direction of interpolation in cases with route.dose == "intravascular" and duration.dose == 0. When direction.out == "before" interpolation occurs only with data before the dose (as is the case for route.dose == "extravascular"), but if direction.out == "after" interpolation occurs from the data after dosing.

Functions

interpolate.conc(): Interpolate concentrations through Tlast (inclusive)
extrapolate.conc(): Extrapolate concentrations after Tlast
interp.extrap.conc.dose(): Interpolate and extrapolate concentrations without interpolating or extrapolating beyond doses.