pk.calc.half.life: Compute the half-life and associated parameters

Description

The terminal elimination half-life is estimated from the final points in the concentration-time curve using semi-log regression (log(conc)~time) with automated selection of the points for calculation (unless manually.selected.points is TRUE).

Usage

pk.calc.half.life(
  conc,
  time,
  tmax,
  tlast,
  manually.selected.points = FALSE,
  options = list(),
  min.hl.points = NULL,
  adj.r.squared.factor = NULL,
  conc.blq = NULL,
  conc.na = NULL,
  first.tmax = NULL,
  allow.tmax.in.half.life = NULL,
  check = TRUE
)

Value

A data frame with one row and columns for

tmax: Time of maximum observed concentration (only included if not given as an input)
tlast: Time of last observed concentration above the LOQ (only included if not given as an input)
r.squared: coefficient of determination
adj.r.squared: adjusted coefficient of determination
lambda.z: elimination rate
lambda.z.time.first: first time for half-life calculation
lambda.z.n.points: number of points in half-life calculation
clast.pred: Concentration at tlast as predicted by the half-life line
half.life: half-life
span.ratio: span ratio [ratio of half-life to time used for half-life calculation

Arguments

conc: Measured concentrations
time: Time of the measurement of the concentrations
tmax: Time of maximum concentration (will be calculated and included in the return data frame if not given)
tlast: Time of last concentration above the limit of quantification (will be calculated and included in the return data frame if not given)
manually.selected.points: Have the input points (conc and time) been manually selected? The impact of setting this to TRUE is that no selection for the best points will be done. When TRUE, this option causes the options of adj.r.squared.factor, min.hl.points, and allow.tmax.in.half.life to be ignored.
options: List of changes to the default PKNCA options (see PKNCA.options())
min.hl.points: The minimum number of points that must be included to calculate the half-life
adj.r.squared.factor: The allowance in adjusted r-squared for adding another point.
conc.blq: See clean.conc.blq()
conc.na: See clean.conc.na()
first.tmax: See pk.calc.tmax().
allow.tmax.in.half.life: Allow the concentration point for tmax to be included in the half-life slope calculation.
check: Run assert_conc_time(), clean.conc.blq(), and clean.conc.na()?

Details

See the "Half-Life Calculation" vignette for more details on the calculation methods used.

If manually.selected.points is FALSE (default), the half-life is calculated by computing the best fit line for all points at or after tmax (based on the value of allow.tmax.in.half.life). The best half-life is chosen by the following rules in order:

At least min.hl.points points included
A lambda.z > 0 and at the same time the best adjusted r-squared (within adj.r.squared.factor)
The one with the most points included

If manually.selected.points is TRUE, the conc and time data are used as-is without any form of selection for the best-fit half-life.

References

Gabrielsson J, Weiner D. "Section 2.8.4 Strategies for estimation of lambda-z." Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications, 4th Edition. Stockholm, Sweden: Swedish Pharmaceutical Press, 2000. 167-9.