Non-compartmental analysis — make

Performs a non-compartmental analysis from a PM_result object using observed concentrations in the raw data file PM_result$data$standard_data or from an individual Bayesian posterior predicted time-observation profiles PM_result$post$data generated automatically after an NPAG run and loaded with PM_load .

Usage

make_NCA(
  x,
  postPred = F,
  include,
  exclude,
  input = 1,
  icen = "median",
  outeq = 1,
  block = 1,
  start = 0,
  end = Inf,
  first = NA,
  last = NA,
  terminal = 3
)

Arguments

x: PM_data object to analyze.
postPred: Boolean switch to use the posterior predictions rather than the observed. concentrations. Default is FALSE. Ignored if an IT2B run is used to supply the raw data file.
include: A vector of subject IDs to include in the NCA, e.g. c(1:3,5,15)
exclude: A vector of subject IDs to exclude in the NCA, e.g. c(4,6:14,16:20). When postPred is TRUE, any subject(s) excluded from the IT2B/NPAG run will be excluded as well.
input: The number of the input (e.g. drug) to analyze; default 1.
icen: If postPred is TRUE, use predictions based on median or mean of each subject's Bayesian posterior parameter distribution. Default is "median", but could be "mean".
outeq: The number of the output equation to analyze; default 1
block: The number of the observation block within subjects, with each block delimited by EVID=4 in the data file; default 1
start: The beginning of the time interval to look for doses and observations, e.g. 120. It can be a vector to allow for individual start times per subject, e.g. c(120,120,144,168). If the length of start is less than the number of subjects, the last value will be recycled as needed. If the start time is not 0 (default), then it is assumed that steady state (multiple dose) conditions apply.
end: Analogous to start, set this equal to the end of the dosing interval. It too can be a vector, with the last value recycled as necessary. Default is Inf, i.e. all data used.
first: Alternative way to specify time interval for NCA by choosing dose number, e.g. 1 or 3. May be a numeric vector, like start and end, e.g. c(1,1,1,3,1,...) to allow for individualization by subject. The last value will be recycled to ensure length equal to the number of subjects. Default is NA, which means start will be used.
last: The complement to first, specifying the last dose to end the time interval. If NA, which is the default, then the maximum time per subject will be the upper bound of the time interval.Like first, last can be a vector, with the last value recycled as necessary. Use NA in the vector to signify maximum time for that subject.
terminal: Number of observations to use for terminal curve fitting (i.e. to estimate k). Default is 3.

Value

A dataframe of class PMnca with columns

id: Subject identification
auc: Area under the time-observation curve, using the trapezoidal approximation, from time 0 until the second dose, or if only one dose, until the last observation
aumc: Area under the first moment curve
k: Slope by least-squares linear regression of the final 3 log-transformed observations vs. time. If the final 3 concentrations are not decreasing such that linear regression results in a positive slope, this value and all others that depend on k will be suppressed.
auclast: Area under the curve from the time of the last observation to infinity, calculated as Final obs/k. This value will be suppressed if start != 0.
aumclast: Area under the first moment curve from the time of the last observation to infinity. This value will be suppressed if start != 0.
aucinf: Area under the curve from time 0 to infinity, caluculated as auc + auclast
aumcinf: Area under the first moment curve from time 0 to infinity
mrt: Mean residence time, calculated as 1/k
cmax: Maximum predicted concentration after the first dose
tmax: Time to cmax
cl: Clearance, calculated as dose/aucinf
vdss: Volume of distribution at steady state, calculated as cl*mrt
thalf: Half life of elimination, calculated as ln(2)/k
dose: Dose for each subject

Details

If concentrations from multiple dose intervals are included in the start to end time interval, make_NCA will superpose the concentrations using the time after dose. An error will be generated if different doses are within this interval as superposition would no longer be valid.

A minimum of 5 concentrations must be available to perform NCA for any given subject. Fewer than this will suppress all results for that subject.

Author

Michael Neely