qpNCA {qpNCA}

Perform Non-compartmental Analysis

Description

Consecutively executes the following NCA steps:

• correct.loq impute LOQ values

• est.thalf calculate lambda_z and half-life

• plot_reg plot each regression curve

• calc.ctmax calculate Cmax and Tmax

• correct.time correct time deviations at critical time points

• correct.conc impute missing concentrations at critical time points

• tab.corr tabulate data alterations

• calc.par calculates parameters not dependent on lambda_z

• calc.par.th calculates parameters dependent on lambda_z

Usage

qpNCA(
  x,
  by = character(0),
  nomtimevar = "ntad",
  timevar = "time",
  depvar = "dv",
  bloqvar = "bloq",
  loqvar = "loq",
  loqrule = 1,
  includeCmax = "Y",
  exclvar = NA,
  plotdir = NA,
  timelab = "timevar",
  deplab = "depvar",
  tau = NA,
  tstart = NA,
  tend = NA,
  teval = NA,
  covariates = NA,
  dose = "dose",
  factor = 1,
  reg = "SD",
  ss = "N",
  route = "EV",
  method = 1
)

Arguments

x

input dataset name

by

column names in x indicating grouping variables

nomtimevar

variable name containing the nominal sampling time after dose

timevar

variable name containing the actual sampling time after dose

depvar

variable name containing the dependent variable (e.g., concentration)

bloqvar

variable name containing the BLOQ flag (0: no, 1: yes)

loqvar

variable name containing the LOQ value

loqrule

rule number to be applied to the LOQ values in the curve; x$loqrule overrides if provided

includeCmax

include Cmax in half-life estimation? (y/n); x$includeCmax overrides if provided

exclvar

variable name indicating points to be excluded in half-life estimation (these should have exclvar = 1)

plotdir

directory where regression plots (.PNG) will be saved; NA gives default location, NULL skips regression plots

timelab

label for time axis in regression plots

deplab

label for dependent variable axis in regression plots

tau

dosing interval (for multiple dosing); NA (default) if single dose; x$tau overrides

tstart

start time of partial AUC (start>0); NA (default) if not requested; x$tstart overrides

tend

end time of partial AUC; NA (default) if not requested; x$tend overrides

teval

user selected AUC interval (starting at t=0); NA (default) if not requested; x$teval overrides

covariates

covariates dataset; Must contain the dose variable

dose

variable containing the dose amount

factor

conversion factor for CL and V calculation (e.g. dose in mg, conc in ng/mL, factor=1000); x$factor overrides if provided

reg

regimen, "SD" or "MD"; x$reg overrides if provided

ss

is steady state reached (y/n); x$ss overrides if provided

route

route of drug administration ("EV","IVB", "IVI"); x$route overrides if provided

method

method for trapezoidal rule; x$method overrides if provided

• 1: linear up - linear down

• 2: linear up - logarithmic down

• 3: linear before first Tmax, logarithmic after first Tmax

Value

(list)

• covariates covariates selected with the covariates argument

• half_life linear regression parameters

• ct_corr the time and concentration corrected dataset

• corrections descriptions of the corrections applied

• pkpar all estimated PK parameters

• plots generated plots

Examples

library(magrittr)
library(dplyr)
library(qpNCA)
x <- Theoph
ntad <- c(0,0.25,0.5,1,2,4,5,7,9,12,24)
for(i in 1:nrow(x)){
  time  <- x$Time[[i]]
  delta <- abs(ntad - time)
  best  <- min(delta)
  index <- match(best, delta)
  nom   <- ntad[[index]]
  x$ntad[[i]] <- nom
}
rm(list = c('time','delta','best','index','nom', 'i','ntad'))
x %<>% rename(time = Time, dv = conc, subject = Subject)
x %<>% mutate(bloq = 0, loq = 0.01, tad = time,excl_th=0,
              subject=as.numeric(subject),ntad=as.numeric(ntad))
x %<>% filter(dv > 0)
covs <- x %>%
  select(subject, Wt, dose = Dose) %>%
  distinct(subject,.keep_all=TRUE) %>%
  mutate(dose = dose * Wt) # see ?Theoph
z <- qpNCA(x, by = 'subject', covariates = covs, exclvar='excl_th')