NCA parameters

The following page describes all the parameters computed by the non compartmental analysis. Parameter names are fixed and cannot be changed.

Parameters related to \(\lambda_z\)

Name PKPARMCD CDISC PKPARM CDISC UNITS DESCRIPTION
Rsq R2 R Squared no unit Goodness of fit statistic for the terminal (log-linear) phase between the linear regression and the data
Rsq_adjusted R2ADJ R Squared Adjusted no unit Goodness of fit statistic for the terminal elimination phase, adjusted for the number of points used in the estimation of \(\lambda_z\)
Corr_XY CORRXY Correlation Between TimeX and Log ConcY no unit Correlation between time (X) and log concentration (Y) for the points used in the estimation of \(\lambda_z\)
No_points_lambda_z LAMZNPT Number of Points for Lambda z no unit Number of points considered in the \(\lambda_z\) regression
Lambda_z LAMZ Lambda z 1/time First order rate constant associated with the terminal (log-linear) portion of the curve. Estimated by linear regression of time vs. log concentration
Lambda_z_lower LAMZLL Lambda z Lower Limit time Lower limit on time for values to be included in the \(\lambda_z\) calculation
Lambda_z_upper LAMZUL Lambda z Upper Limit time Upperlimit on time for values to be included in the \(\lambda_z\) calculation
HL_Lambda_z LAMZHL Half-Life Lambda z time Terminal half-life
= ln(2)/Lambda_z
Lambda_z_intercept no unit Intercept found during the regression for (\lambda_z\), i.e. value of the regression (in log-scale) at time 0, i.e. the regression writes
log(Concentration) = -Lambda_z*t+Lambda_z_intercept
Span no unit Ratio between the sampling interval of the measurements used for the \(\lambda_z\) and the terminal half-life
= (Lambda_z_upper – Lambda_z_lower)*Lambda_z/ln(2)

Parameters related to plasma/blood measurements

Name PKPARMCD CDISC PKPARM CDISC UNITS DESCRIPTION
Tlag TLAG Time Until First Nonzero Conc time temps entre la dose et le dernier temps après la dose où OBS=0 ou OBS=LOQ Tlag is the time prior to the first measurable (non-zero) concentration. Tlag is 0 if the first observation after the last dose is not 0 or LOQ. The value is set to 0 for non extravascular input
T0 time Time of the dose
Dose amount Amount of the dose
N_Samples no unit Number of samples in the individuals.
C0 C0 Initial Conc amount/volume If a PK profile does not contain an observation at dose time (C0), the following value is added
Extravascular and Infusion data. For single dose data, a concentration of zero.  For steady-state, the minimum observed during the dose interval.
IV Bolus data. Log-linear regression of first two data points to back-extrapolate C0.
Tmin TMIN Time of CMIN Observation time Time of minimum concentration sampled during a dosing interval.
Cmin CMIN Min Conc amount/volume Minimum observed concentration, occurring at Tmin. If not unique, then the first minimum is used.
Tmax TMAX Time of CMAX time Time of maximum observed concentration.
– For non-steady-state data, the entire curve is considered.
– For steady-state data, Tmax corresponds to points collected during a dosing interval.
If the maximum observed concentration is not unique, then the first maximum is used.
Cmax CMAX Max Conc amount/volume Maximum observed concentration, occurring at Tmax. If not unique, then the first maximum is used.
Cmax_D CMAXD Max Conc Norm by Dose 1/volume Maximum observed concentration divided by dose.
Cmax_D = Cmax/Dose
Tlast TLST Time of Last Nonzero Conc time Last time point with measurable concentration
Clast CLST Last Nonzero Conc amount/volume Concentration of last time point with measurable concentration
AUClast AUCLST AUC to Last Nonzero Conc time.amount/volume Area under the curve from the time of dosing to the last measurable positive concentration. The calculation depends on the Integral method setting.
AUClast_D AUCLSTD AUC to Last Nonzero Conc Norm by Dose time/volume Area under the curve from the time of dosing to the last measurable concentration divided by the dose.
AUClast_D = AUClast/Dose
AUMClast AUMCLST AUMC to Last Nonzero Conc time2.amount/volume Area under the moment curve from the time of dosing to the last measurable concentration.
MRTlast MRTIVLST MRT Intravasc to Last Nonzero Conc time [if intravascular] Mean residence time from the time of dosing to the time of the last measurable concentration, for a substance administered by intravascular dosing.
MRTlast_iv = AUMClast/AUClast – TI/2, where TI represents infusion duration.
MRTlast MRTEVLST MRT Extravasc to Last Nonzero Conc time [if extravascular] Mean residence time from the time of dosing to the time of the last measurable concentration for a substance administered by extravascular dosing.
MRTlast_ev = AUMClast/AUClast – TI/2, where TI represents infusion duration.
AUCall AUCALL AUC All time.amount/volume Area under the curve from the time of dosing to the time of the last observation.
If the last concentration is positive AUClast=AUCall.
Otherwise, AUCall will not be equal to AUClast as it includes the additional area from the last measurable concentration down to zero or negative observations.
AUCINF_obs AUCIFO AUC Infinity Obs time.amount/volume AUC from Dosing_time extrapolated to infinity, based on the last observed concentration.
AUCINF_obs = AUClast + Clast/Lambda_z
AUCINF_D_obs AUCIFOD AUC Infinity Obs Norm by Dose time/volume AUCINF_obs divided by dose
AUCINF_D_obs = AUCINF_obs/Dose
AUC_%Extrap_obs AUCPEO AUC %Extrapolation Obs % Percentage of AUCINF_obs due to extrapolation from Tlast to infinity.
AUC_%Extrap_obs = 100*(1- AUClast / AUCINF_obs)
AUC_%Back_Ext_obs AUCPBEO AUC %Back Extrapolation Obs % Applies only for intravascular bolus dosing. the percentage of AUCINF_obs that was due to back extrapolation to estimate C(0).
AUMCINF_obs AUMCIFO AUMC Infinity Obs time2.amount/volume Area under the first moment curve to infinity using observed Clast
AUMCINF_obs = AUMClast + (Clast/Lambda_z)*(Tlast + 1.0/Lambda_z)
AUMC_%Extrap_obs AUMCPEO AUMC % Extrapolation Obs % Extrapolated (% or total) area under the first moment curve to infinity using observed Clast
AUMC_%Extrap_obs = 100*(1- AUMClast / AUMCINF_obs)
MRTINF_obs MRTIVIFO MRT Intravasc Infinity Obs time [if intravascular] Mean Residence Time extrapolated to infinity for a substance administered by intravascular dosing using observed Clast
MRTINF_obs_iv = AUMCINF_obs/AUCINF_obs- TI/2, where TI represents infusion duration.
MRTINF_obs MRTEVIFO MRT Extravasc Infinity Obs time [if extravascular] Mean Residence Time extrapolated to infinity for a substance administered by extravascular dosing using observed Clast
MRTINF_obs_ev = AUMCINF_obs/AUCINF_obs- TI/2, where TI represents infusion duration.
Vz_F_obs VZFO Vz Obs by F volume [if extravascular] Volume of distribution associated with the terminal phase divided by F (bioavailability)
Vz_F_obs = Dose/Lambda_z/AUCINF_obs
Cl_F_obs CLFO Total CL Obs by F volume/time [if extravascular] Clearance over F (based on observed Clast)
Cl_F_obs = Dose/AUCINF_obs
Vz_obs VZO Vz Obs volume [if intravascular] Volume of distribution associated with the terminal phase
Vz_obs= Dose/Lambda_z/AUCINF_obs
Cl_obs CLO Total CL Obs volume/time  [if intravascular] Clearance (based on observed Clast)
Cl_obs = Dose/AUCINF_obs
Vss_obs VSSO Vol Dist Steady State Obs volume  [if extravascular] An estimate of the volume of distribution at steady state based last observed concentration.
Vss_obs = MRTINF_obs*Cl_obs
Clast_pred amount/volume Clast_pred = exp(Lambda_z_intercept- Lambda_z* Tlast)
The values alpha (corresponding to the y-intercept obtained when calculating \(\lambda_z\)) and lambda_z are those values found during the regression
for \(\lambda_z\)
AUCINF_pred AUCIFP AUC Infinity Pred time.amount/volume Area under the curve from the dose time extrapolated to infinity, based on the last predicted concentration, i.e., concentration at the final observation time estimated using the linear regression performed to estimate \(\lambda_z\) .
AUCINF_pred = AUClast + Clast_pred/Lambda_z
AUCINF_D_pred AUCIFPD AUC Infinity Pred Norm by Dose time/volume AUCINF_pred divided by dose
= AUCINF_pred/Dose
AUC_%Extrap_pred AUCPEP AUC %Extrapolation Pred % Percentage of AUCINF_pred due to extrapolation from Tlast to infinity
AUC_%Extrap_pred = 100*(1- AUClast / AUCINF_pred)
AUC_%Back_Ext_pred AUCPBEP AUC %Back Extrapolation Pred % Applies only for intravascular bolus dosing. The percentage of AUCINF_pred that was due to back extrapolation to estimate C(0).
AUMCINF_pred AUMCIFP AUMC Infinity Pred time2.amount/volume Area under the first moment curve to infinity using predicted Clast
AUMCINF_pred = AUMClast + (Clast_pred/Lambda_z)*(Tlast+1/Lambda_z)
AUMC_%Extrap_pred AUMCPEP AUMC % Extrapolation Pred % Extrapolated (% or total) area under the first moment curve to infinity using predicted Clast
AUMC_%Extrap_pred = 100*(1- AUMClast / AUMCINF_pred)
MRTINF_pred MRTIVIFP MRT Intravasc Infinity Pred time [if intravascular] Mean Residence Time extrapolated to infinity for a substance administered by intravascular dosing using predicted Clast
MRTINF_pred MRTEVIFP MRT Extravasc Infinity Pred time [if extravascular] Mean Residence Time extrapolated to infinity for a substance administered by extravascular dosing using predicted Clast
Vz_F_pred VZFP Vz Pred by F volume [if extravascular] Volume of distribution associated with the terminal phase divided by F (bioavailability)
= Dose/Lambda_z/AUCINF_pred
Cl_F_pred CLFP Total CL Pred by F volume/time [if extravascular] Clearance over F (using predicted Clast)
Cl_F_pred = Dose/AUCINF_pred
Vz_pred VZP Vz Pred volume [if intravascular] Volume of distribution associated with the terminal phas
Vz_pred = Dose/Lambda_z/AUCINF_pred
Cl_pred CLP Total CL Pred volume/time [if intravascular] Clearance (using predicted Clast)
= Dose/AUCINF_pred
Vss_pred VSSP Vol Dist Steady State Pred volume [if intravascular] An estimate of the volume of distribution at steady state based on the last predicted concentration.
Vss_pred = MRTINF_pred*Cl_pred
AUC_lower_upper AUCINT AUC from T1 to T2 time.amount/volume AUC from T1 to T2 (partial AUC)
AUC_lower_upper_D AUCINTD AUC from T1 to T2 Norm by Dose time/volume AUC from T1 to T2 (partial AUC) divided by Dose
CAVG_lower_upper CAVGINT Average Conc from T1 to T2 amount/volume Average concentration from T1 to T2

 

Parameters related to plasma/blood measurements specific to steady state dosing regimen

In the case of repeated doses, dedicated parameters are used to define the steady state parameters and some specific formula should be considered for the clearance and the volume for example. Notice that all the calculation dedicated to the area under the first moment curve (AUMC) are not relevant.

Name PKPARMCD CDISC PKPARM CDISC UNITS DESCRIPTION
Tau time The (assumed equal) dosing interval for steady-state data.
Ctau CTROUGH Conc Trough amount/volume Concentration at end of dosing interval.
If the observed concentration does not exist, the value is interpolated or extrapolated.
AUC_TAU AUCTAU AUC Over Dosing Interval time.amount/volume The area under the curve (AUC) for the defined interval between doses (TAU). The calculation depends on the Integral method setting.
AUC_TAU_D AUCTAUD AUC Over Dosing Interval Norm by Dose time/volume The area under the curve (AUC) for the defined interval between doses (TAU) divided by the dose.
AUC_TAU_D = AUC_TAU/Dose
AUC_TAU_%Extrap %
 Percentage of AUC due to extrapolation in steady state.
 AUC_TAU_%Extrap = 100*(AUC [Tlast, tau] if Tlast<=tau)/AUC_TAU;
AUMC_TAU AUMCTAU AUMC Over Dosing Interval time2.amount/volume The area under the first moment curve (AUMC) for the defined interval between doses (TAU).
Vz_F VZFTAU Vz for Dose Int by F volume [if extravascular] The volume of distribution associated with the terminal slope following extravascular administration divided by the fraction of dose absorbed, calculated using AUC_TAU.
Vz_F =  Dose/Lambda_z/AUC_TAU 
Vz VZTAU Vz for Dose Int volume [if intravascular] The volume of distribution associated with the terminal slope following intravascular administration, calculated using AUC_TAU.
Vz =  Dose/Lambda_z/AUC_TAU 
CLss_F CLFTAU Total CL by F for Dose Int volume/time [if extravascular] The total body clearance for extravascular administration divided by the fraction of dose absorbed, calculated using AUC_TAU .
CLss_F =  Dose/AUC_TAU 
CLss CLTAU Total CL for Dose Int volume/time [if intravascular] The total body clearance for intravascular administration, calculated using AUC_TAU.
CLss =  Dose/AUC_TAU 
Cavg CAVG Average Concentration amount/volume AUCTAU divided by Tau.
Cavg = AUC_TAU /Tau
Fluctuation% FLUCP Fluctuation% % The difference between Cmin and Cmax standardized to Cavg, between dose time and Tau.
Fluctuation%  = 100.0* (Cmax -Cmin)/Cavg 
Fluctuation%_Tau % The difference between Ctau and Cmax standardized to Cavg, between dose time and Tau.
Fluctuation% _Tau  = 100.0* (Cmax -Ctau)/Cavg
Accumulation_Index AILAMZ Accumulation Index using Lambda z no unit Theoretical accumulation ratio: Predicted accumulation ratio for area under the curve (AUC) calculated using the Lambda z estimated from single dose data.
Accumulation_Index = 1.0/(1.0 -exp(-Lambda_z*Tau))
Swing no unit The degree of fluctuation over one dosing interval at steady state
Swing = (Cmax -Cmin)/Cmin
Swing_Tau no unit Swing_Tau = (Cmax -Ctau)/Ctau
Tmin TMIN Time of CMIN observation. time Time of minimum concentration sampled during a dosing interval.
Cmin CMIN Min Conc amount/volume Minimum observed concentration between dose time and dose time + Tau.
Cmax CMAX Max Conc amount/volume Maximum observed concentration between dose time and dose time + Tau.
MRTINF_obs MRTIVIFO or MRTEVIFO MRT Intravasc Infinity Obs or MRT Extravasc Infinity Obs time Mean Residence Time extrapolated to infinity using predicted Clast, calculated using AUC_TAU.

 

Parameters related to urine measurements

Name PKPARMCD CDISC PKPARM CDISC UNITS DESCRIPTION
T0 time Time of the last administered dose (assumed to be zero unless
otherwise specified).
Dose amount Amount of the dose
N_Samples no unit Number of samples in the individuals.
Tlag TLAG Time Until First Nonzero Conc time Midpoint prior to the first measurable (non-zero) rate.
Tmax_Rate ERTMAX Midpoint of Interval of Maximum ER time Midpoint of collection interval associated with the maximum observed excretion rate.
Max_Rate ERMAX Max Excretion Rate amount/time Maximum observed excretion rate.
Mid_Pt_last ERTLST Midpoint of Interval of Last Nonzero ER time Midpoint of collection interval associated with Rate_last.
Rate_last ERLST Last Meas Excretion Rate amount/time Last measurable (positive) rate.
AURC_last AURCLST AURC to Last Nonzero Rate amount Area under the urinary excretion rate curve from time 0 to the last
measurable rate.
AURC_last_D AURCLSTD AURC to Last Nonzero Rate Norm by Dose no unit The area under the urinary excretion rate curve (AURC) from time zero to the last measurable rate, divided by the dose.
Vol_UR VOLPK Sum of Urine Vol volume Sum of Urine Volumes
Amount_Recovered amount Cumulative amount eliminated.
Percent_Recovered % 100*Amount_Recovered/Dose
AURC_all AURCALL AURC All amount Area under the urinary excretion rate curve from time 0 to the last rate. This equals AURC_last if the last rate is measurable.
AURC_INF_obs AURCIFO AURC Infinity Obs amount Area under the urinary excretion rate curve extrapolated to infinity, based on the last observed excretion rate.
AURC_%Extrap_obs AURCPEO AURC % Extrapolation Obs % Percent of AURC_INF_obs that is extrapolated
AURC_INF_pred AURCIFP AURC Infinity Pred amount Area under the urinary excretion rate curve extrapolated to infinity, based on the last predicted excretion rate.
AURC_%Extrap_pred AURCPEP AURC % Extrapolation Pred % Percent of AURC_INF_pred that is extrapolated
AURC_lower_upper AURCINT AURC from T1 to T2 (partial AUC) amount The area under the urinary excretion rate curve (AURC) over the interval from T1 to T2.
Rate_last_pred amount/time The values alpha and Lambda_z are those values found during the regression
for lambda_z