pk.calc.auxc {PKNCA}

A compute the Area Under the (Moment) Curve

Description

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

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.

Value

A numeric value for the AU(M)C.

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.

See Also

clean.conc.blq()

Other AUC calculations: pk.calc.aucint()

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))
pk.calc.auc(myconc, mytime, interval=c(0, Inf))