est.nca: Estimates individual NCA metrics from concentration vs time data. data.

Description

est.nca estimates a comprehensive set of NCA metrics for a given individual using concentration vs time profile.

Usage

est.nca(time, conc, backExtrp = "FALSE", negConcExcl = "FALSE",
  doseType = "ns", adminType = "extravascular", doseNm = NULL,
  dose = NULL, doseNumber = NULL, doseAmt = NULL, method = "linear",
  AUCTimeRange = NULL, LambdaTimeRange = NULL, LambdaExclude = NULL,
  Tau = NULL, TI = NULL, simFile = NULL, dset = "obs")

Arguments

time

Numeric array for time

conc

Numeric array for concentration

backExtrp

If back-extrapolation is needed for AUC (TRUE or FALSE) ("FALSE")

negConcExcl

Exclude -ve conc ("FALSE")

doseType

Steady-state (ss) or nonsteady-state (ns) dose ("ns")

adminType

Route of administration (iv-bolus,iv-infusion,ss,extravascular) ("extravascular")

doseNm

Column name to specify dose identifiers ("NULL")

dose

Dose identifiers used in the entire data (c(1,2)) ("NULL")

doseNumber

Dose identifier used in this estimation (1) ("NULL")

doseAmt

Dose amounts ("NULL")

method

linear, loglinear or mixed ("linear")

AUCTimeRange

User-defined window of time used to estimate AUC ("NULL")

LambdaTimeRange

User-defined window of time to estimate elimination rate-constant ("NULL")

LambdaExclude

User-defined excluded observations during estimation of elimination rate-constant ("NULL")

Tau

Dosing interval for steady-state data ("NULL")

Infusion duration ("NULL")

simFile

Name of the simulated concentration-time data if present ("NULL")

dset

Type, i.e., observed or simulated concentration-time data set ("obs" or "sim") ("obs")

Value

An array of estimated NCA metrics

Details

est.nca estimates a comprehensive set of NCA metrics using the concentration-time profile of an individual. NCA metrics are eatimated according to traditional PK calculations. The names of the various NCA metrics estimated in this package are assigned mainly following the names used in WinNonlin. This package accepts any of the three different types of drug administration, (i) iv-bolus, (ii) iv-infusion and (iii) extravascular; ncappc also can accept both non-steady state and steady-state data. The NCA metrics that are estimated and reported by ncappc are listed below.

C0is the initial concentration at the dosing time. It is the observed concentration at the dosing time, if available. Otherwise it is approximated using the following rules.
Cmax, Tmax and Cmax_Dare the value and the time of maximum observed concentration, respectively. If the maximum concentration is not unique, the first maximum is used. For steady state data, The maximum value between the dosing intervals is considered. Cmax_D is the dose normalized maximum observed concentration.
Clast and Tlastare the last measurable positive comcentration and the corresponding time, respectively.
AUClastis the area under the concentration vs. time curve from the first observed to last measurable concentration.
AUMClastis the first moment of the concentration vs. time curve from the first observed to last measurable concentration.
MRTlastis the mean residence time from the first observed to last measurable concentration.
No_points_Lambda_zis the number of observed data points used to determine the best fitting regression line in the elimination phase.
AUC_pBack_Extis the percentage of AUClast that is contributed by the back extrapolation to estimate C0.
AUClower_upperis the AUC under the concentration-time profile within the user-specified window of time privided as the "AUCTimeRange" argument. In case of empty "AUCTimeRange" argument, AUClower_upper is equal to the AUClast.
Rsq, Rsq_adjusted and Corr_XYare regression coefficient of the regression line used to estimate the elimination rate constant, the adjusted value of Rsq and the square root of Rsq, respectively.
Lambda_zis the elimination rate constant estimated from the regression line representing the terminal phase of the concentration-time prifile.
Lambda_lower and Lambda_upperare the lower and upper limit of the time values from the concentration-time profile used to estimate Lambda_z, respectively, in case the "LambdaTimeRange" is used to specify the time range.
HL_Lambda_zis terminal half-life of the drug.
AUCINF_obs and AUCINF_obs_Dare AUC estimated from the first sampled data extrapolated to infinity and its dose normalized version, respectively. The extrapolation in the terminal phase is based on the last observed concentration Clast_obs.
AUC_pExtrap_obsis the percentage of the AUCINF_obs that is contributed by the extrapolation from the last sampling time to infinity.
AUMCINF_obsis AUMC estimated from the first sampled data extrapolated to infinity. The extrapolation in the terminal phase is based on the last observed concentration.
AUMC_pExtrap_obsis the percentage of the AUMCINF_obs that is contributed by the extrapolation from the last sampling time to infinity.
Vz_obsis the volume of distribution estimated based on total AUC
Cl_obsis total body clearance.
AUCINF_pred and AUCINF_pred_Dare AUC from the first sampled data extrapolated to infinity and its dose normalized version, respectively. The extrapolation in the terminal phase is based on the last predicted concentration obtained from the regression line used to estimate Lambda_z (Clast_pred).
AUC_pExtrap_predis the percentage of the AUCINF_pred that is contributed by the extrapolation from the last sampling time to infinity.
AUMCINF_predis AUMC estimated from the first sampled data extrapolated to infinity. The extrapolation in the terminal phase is based on the last predicted concentration obtained from the regression line used to estimate Lambda_z (Clast_pred).
AUMC_pExtrap_predis the percentage of the AUMCINF_pred that is contributed by the extrapolation from the last sampling time to infinity.
Vz_predis the volume of distribution estimated based on AUCINF_pred.
Cl_predis the total body clearance estimated based on AUCINF_pred.
MRTINF_obsis the mean residence time from the first sampled time extrapolated to infinity based on the last observed concentration (Clast_obs).
MRTINF_predis the mean residence time from the first sampled time extrapolated to infinity based on the last predicted concentration obtained from the regression line used to estimate Lambda_z (Clast_pred).
Vss_obs and Vss_predare estimated volume of distribution at steady-state based on Clast_obs and Clast_pred, respectively.
Tauis the dosing interval for steady-state data. This value is assumed equarion over multiple doses.
Cmin and Tminare the minimum concentration between 0 and Tau and the corresponding time, respectively.
Cavgis the average concentration between 0 and Tau for steady-state data.
p_Fluctuationis the percentage of the fluctuation of the concentration between 0 and Tau for steady-state data.
Accumulation_Indexis$1/(1-e^(-\lambda_z*\tau))$
Clssis an estimate of the total body clearance for steady-state data.