A compute the Area Under the (Moment) Curve

Compute the area under the curve (AUC) and the area under the moment curve (AUMC) for pharmacokinetic (PK) data. AUC and AUMC are used for many purposes when analyzing PK in drug development.

Usage

pk.calc.auxc(
  conc,
  time,
  interval = c(0, Inf),
  clast = pk.calc.clast.obs(conc, time, check = FALSE),
  lambda.z = NA,
  auc.type = c("AUClast", "AUCinf", "AUCall"),
  options = list(),
  method = NULL,
  conc.blq = NULL,
  conc.na = NULL,
  check = TRUE,
  fun_linear,
  fun_log,
  fun_inf
)

pk.calc.auc(conc, time, ..., options = list())

pk.calc.auc.last(conc, time, ..., options = list())

pk.calc.auc.inf(conc, time, ..., options = list(), lambda.z)

pk.calc.auc.inf.obs(conc, time, clast.obs, ..., options = list(), lambda.z)

pk.calc.auc.inf.pred(conc, time, clast.pred, ..., options = list(), lambda.z)

pk.calc.auc.all(conc, time, ..., options = list())

pk.calc.aumc(conc, time, ..., options = list())

pk.calc.aumc.last(conc, time, ..., options = list())

pk.calc.aumc.inf(conc, time, ..., options = list(), lambda.z)

pk.calc.aumc.inf.obs(conc, time, clast.obs, ..., options = list(), lambda.z)

pk.calc.aumc.inf.pred(conc, time, clast.pred, ..., options = list(), lambda.z)

pk.calc.aumc.all(conc, time, ..., options = list())

Arguments

conc: Measured concentrations
time: Time of the measurement of the concentrations
interval: Numeric vector of two numbers for the start and end time of integration
clast, clast.obs, clast.pred: The last concentration above the limit of quantification; this is used for AUCinf calculations. If provided as clast.obs (observed clast value, default), AUCinf is AUCinf,obs. If provided as clast.pred, AUCinf is AUCinf,pred.
lambda.z: The elimination rate (in units of inverse time) for extrapolation
auc.type: The type of AUC to compute. Choices are 'AUCinf', 'AUClast', and 'AUCall'.
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')
conc.blq: How to handle BLQ values in between the first and last above LOQ concentrations. (See clean.conc.blq() for usage instructions.)
conc.na: How to handle missing concentration values. (See clean.conc.na() for usage instructions.)
check: Run assert_conc_time(), clean.conc.blq(), and clean.conc.na()?
fun_linear: The function to use for integration of the linear part of the curve (not required for AUC or AUMC functions)
fun_log: The function to use for integration of the logarithmic part of the curve (if log integration is used; not required for AUC or AUMC functions)
fun_inf: The function to use for extrapolation from the final measurement to infinite time (not required for AUC or AUMC functions.
...: For functions other than pk.calc.auxc, these values are passed to pk.calc.auxc

Value

A numeric value for the AU(M)C.

Details

pk.calc.auc.last is simply a shortcut setting the interval parameter to c(0, "last").

Extrapolation beyond Clast occurs using the half-life and Clast,obs; Clast,pred is not yet supported.

If all conc input are zero, then the AU(M)C is zero.

Functions

pk.calc.auc(): Compute the area under the curve
pk.calc.auc.last(): Compute the AUClast.
pk.calc.auc.inf(): Compute the AUCinf
pk.calc.auc.inf.obs(): Compute the AUCinf with the observed Clast.
pk.calc.auc.inf.pred(): Compute the AUCinf with the predicted Clast.
pk.calc.auc.all(): Compute the AUCall.
pk.calc.aumc(): Compute the area under the moment curve
pk.calc.aumc.last(): Compute the AUMClast.
pk.calc.aumc.inf(): Compute the AUMCinf
pk.calc.aumc.inf.obs(): Compute the AUMCinf with the observed Clast.
pk.calc.aumc.inf.pred(): Compute the AUMCinf with the predicted Clast.
pk.calc.aumc.all(): Compute the AUMCall.

References

Gabrielsson J, Weiner D. "Section 2.8.1 Computation methods - Linear trapezoidal rule." Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications, 4th Edition. Stockholm, Sweden: Swedish Pharmaceutical Press, 2000. 162-4.

Gabrielsson J, Weiner D. "Section 2.8.3 Computation methods - Log-linear trapezoidal rule." Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications, 4th Edition. Stockholm, Sweden: Swedish Pharmaceutical Press, 2000. 164-7.

Examples

myconc <- c(0, 1, 2, 1, 0.5, 0.25, 0)
mytime <- c(0, 1, 2, 3, 4,   5,    6)
pk.calc.auc(myconc, mytime, interval=c(0, 6))
#> [1] 4.524716
pk.calc.auc(myconc, mytime, interval=c(0, Inf))
#> [1] 4.524716