Parameters

Rsq

R squared

R2

unitless

Goodness of fit statistic for the λz regression

Rsq = 1 - sum(log(Conc) - pred) / sum(log(Conc)-mean(log(Conc)))

Rsq_adjusted

adjusted R squared

R2ADJ

unitless

Goodness of fit statistic for the λz regression, adjusted for the number of points

Rsq_adjusted = 1 - (1 - Rsq) * (No_points_lambda_z - 1) / (No_points_lambda_z - 2)

Corr_XY

Correlation

CORRXY

unitless

Correlation between time (X) and log concentration (Y) for the points used in the estimation of λz

Corr_XY = sqrt(Rsq)

No_points_lambda_z

Number of points

LAMZNPT

unitless

Number of points considered in the λz regression

_

Lambda_z

k_el

LAMZ

1/time

First order rate constant associated with the terminal elimination phase for concentration data

Obtained from the λz linear regression
log(Conc) = Lambda_z_intercept - Lambda_z*t

Lambda_z_lower

k_el Lower

LAMZLL

time

Lower limit on time for values to be included in the λz calculation

_

Lambda_z_upper

k_el Upper

LAMZUL

time

Upper limit on time for values to be included in the λz calculation

_

HL_Lambda_z

T_1/2

LAMZHL

time

Terminal half-life

HL_Lambda_z = ln(2)/Lambda_z

Lambda_z_intercept

Intercept

–

unitless

Intercept of the λz regression, i.e. value of the regression (in log-scale) at time 0.

Obtained from the λz linear regression
log(Conc) = Lambda_z_intercept - Lambda_z*t

Span

Span

–

unitless

Ratio between the sampling interval of the measurements used for the λz and the terminal half-life

Span = (Lambda_z_upper - Lambda_z_lower) / HL_Lambda_z

Tlag

T_lag

TLAG

time

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.

[if intravenous]
Tlag = 0
[if extravascular]
Tlag =

T0

T₀

time

Time of the dose

_

Dose

Dose

amount

Amount of the dose

_

N_Samples

Number of samples

–

unitless

Number of samples in the individuals (including zero or negative concentrations and BLQ not considered as “missing”)

_

C0

C₀

C0

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.

Tmax

T_max

TMAX

time

Time of maximum observed concentration.

[For non-steady-state data]
all points are considered.
[For steady-state data]
only points within the dosing interval (bounds included) are considered
If the maximum observed concentration is not unique, then the first maximum is used.

Cmax

C_max

CMAX

amount/

volume

Maximum observed concentration, occurring at Tmax.

[For non-steady-state data]
all points are considered.
[For steady-state data]
only points within the dosing interval (bounds included) are considered
If the maximum observed concentration is not unique, then the first maximum is used.

Cmax_D

C_max/Dose

CMAXD

1/volume

Maximum observed concentration divided by dose.

Cmax_D = Cmax/Dose

Tlast

T_last

TLST

time

Last time point with measurable concentration

Clast

C_last

CLST

amount/

volume

Concentration of last time point with measurable concentration

AUClast

AUC_0-tlast

AUCLST

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.

See

AUClast_D

AUC_0-tlast/Dose

AUCLSTD

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

AUMC_0-tlast

AUMCLST

time²⋅amount/volume

Area under the moment curve (area under the curve of the product of concentration and time versus time) from the time of dosing to the last measurable concentration.

See “AUC calculation” for details

MRTlast

MRT_last

MRTIVLST

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

MRT_last

MRTEVLST

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

AUC_all

AUCALL

time⋅amount/volume

Area under the curve from the time of dosing to the time of the last observation.

See “AUC calculation” for details.

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

AUC_0-inf

AUCIFO

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

AUC_{0-inf, pred}

AUCIFOD

time/volume

AUCINF_obs divided by dose
AUCINF_D_obs = AUCINF_obs/Dose

AUC_PerCentExtrap_obs

% extrapolated AUC

AUCPEO

%

Percentage of AUCINF_obs due to extrapolation from Tlast to infinity.
AUC_%Extrap_obs = 100*(1- AUClast / AUCINF_obs)

AUC_PerCentBack_Ext_obs

% AUC backextrapolated

AUCPBEO

%

Applies only for intravascular bolus dosing. the percentage of AUCINF_obs that was due to back extrapolation to estimate C(0).

AUMCINF_obs

AUMC_0-inf

AUMCIFO

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_PerCentExtrap_obs

% extrapolated AUMC

AUMCPEO

%

Extrapolated (% or total) area under the first moment curve to infinity using observed Clast
AUMC_%Extrap_obs = 100*(1- AUMClast / AUMCINF_obs)

MRTINF_obs

MRT_0-inf

MRTIVIFO

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

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

Vz_F_obs

V_d/F

VZFO

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

CL/F

CLFO

volume/time

[if extravascular] Clearance over F (based on observed Clast)
Cl_F_obs = Dose/AUCINF_obs

Vz_obs

V_d

VZO

volume

[if intravascular] Volume of distribution associated with the terminal phase
Vz_obs= Dose/Lambda_z/AUCINF_obs

Cl_obs

CL

CLO

volume/time

 [if intravascular] Clearance (based on observed Clast)
Cl_obs = Dose/AUCINF_obs

Vss_obs

V_ss

VSSO

volume

 [if intravascular] An estimate of the volume of distribution at steady state based last observed concentration.
Vss_obs = MRTINF_obs*Cl_obs

Clast_pred

C_tlast

–

amount/volume

Clast_pred = exp(Lambda_z_intercept- Lambda_z* Tlast)
The values alpha (corresponding to the y-intercept obtained when calculating λz) and lambda_z are those values found during the regression
for λz

AUCINF_pred

AUC_{0-inf, pred}

AUCIFP

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 λz.
AUCINF_pred = AUClast + Clast_pred/Lambda_z

AUCINF_D_pred

AUC_{0-inf, pred}/Dose

AUCIFPD

time/volume

AUCINF_pred divided by dose
= AUCINF_pred/Dose

AUC_PerCentExtrap_pred

% extrapolated AUC_pred

AUCPEP

%

Percentage of AUCINF_pred due to extrapolation from Tlast to infinity
AUC_%Extrap_pred = 100*(1- AUClast / AUCINF_pred)

AUC_PerCentBack_Ext_pred

% AUC backextrapolated_pred

AUCPBEP

%

Applies only for intravascular bolus dosing. The percentage of AUCINF_pred that was due to back extrapolation to estimate C(0).

AUMCINF_pred

AUMC_{0-inf, pred}

AUMCIFP

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_PerCentExtrap_pred

% extrapolated AUMC_pred

AUMCPEP

%

Extrapolated (% or total) area under the first moment curve to infinity using predicted Clast
AUMC_%Extrap_pred = 100*(1- AUMClast / AUMCINF_pred)

MRTINF_pred

MRT_{0-inf, pred}

MRTIVIFP

time

[if intravascular] Mean Residence Time extrapolated to infinity for a substance administered by intravascular dosing using predicted Clast

MRTINF_pred

MRTEVIFP

time

[if extravascular] Mean Residence Time extrapolated to infinity for a substance administered by extravascular dosing using predicted Clast

Vz_F_pred

V_{d, pred}/F

VZFP

volume

[if extravascular] Volume of distribution associated with the terminal phase divided by F (bioavailability)
= Dose/Lambda_z/AUCINF_pred

Cl_F_pred

CL/F_pred

CLFP

volume/time

[if extravascular] Clearance over F (using predicted Clast)
Cl_F_pred = Dose/AUCINF_pred

Vz_pred

V_d,pred

VZP

volume

[if intravascular] Volume of distribution associated with the terminal phas
Vz_pred = Dose/Lambda_z/AUCINF_pred

Cl_pred

CL_pred

CLP

volume/time

[if intravascular] Clearance (using predicted Clast)
= Dose/AUCINF_pred

Vss_pred

V_{ss, pred}

VSSP

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_T1_T2

AUC_t1-t2

AUCINT

time⋅amount/volume

AUC from T1 to T2 (partial AUC)

AUC_T1_T2_D

AUC_t1-t2 /Dose

AUCINTD

time/volume

AUC from T1 to T2 (partial AUC) divided by Dose

CAVG_T1_T2

C_{avg t1-t2}

CAVGINT

amount/volume

Average concentration from T1 to T2

Tau

Tau

–

time

The (assumed equal) dosing interval for steady-state data.

Ctau

C_tau

CTAU

amount/volume

Concentration at end of dosing interval.
If the observed concentration does not exist, the value is interpolated. It it cannot be interpolated, it is extrapolated using lambda_z. If lambda_z has not been computed, it is extrapolated as the last observed value.

Ctrough

C_trough

CTROUGH

amount/volume

Concentration at end of dosing interval.
If the observed concentration does not exist, the value is NaN.

AUC_TAU

AUC_tau

AUCTAU

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

AUC_tau/Dose

AUCTAUD

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_PerCentExtrap

% extrapolated AUC_tau

–

%

 Percentage of AUC due to extrapolation in steady state.

 AUC_TAU_%Extrap = 100*(AUC [Tlast, tau] if Tlast<=tau)/AUC_TAU;

AUMC_TAU

AUMC_tau

AUMCTAU

time²⋅amount/volume

The area under the first moment curve (AUMC) for the defined interval between doses (TAU).

Vz_F

V_d/F or V_{d, SS}/F

VZFTAU

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

V_d or V_{d, SS}

VZTAU

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

CL_ss/F

CLFTAU

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

CL_ss

CLTAU

volume/time

[if intravascular] The total body clearance for intravascular administration, calculated using AUC_TAU.
CLss =  Dose/AUC_TAU 

Cavg

C_avg

CAVG

amount/volume

AUCTAU divided by Tau.
Cavg = AUC_TAU /Tau

FluctuationPerCent

(C_max-C_min)/C_avg %

FLUCP

%

The difference between Cmin and Cmax standardized to Cavg, between dose time and Tau.
Fluctuation%  = 100.0* (Cmax -Cmin)/Cavg 

FluctuationPerCent_Tau

(C_max-C_tau)/C_avg %

–

%

The difference between Ctau and Cmax standardized to Cavg, between dose time and Tau.
Fluctuation% _Tau  = 100.0* (Cmax -Ctau)/Cavg

Accumulation_Index

Accumulation index

AILAMZ

unitless

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

(C_max-C_min)/C_min

–

unitless

The degree of fluctuation over one dosing interval at steady state
Swing = (Cmax -Cmin)/Cmin

Swing_Tau

(C_max-C_tau)/C_tau

–

unitless

Swing_Tau = (Cmax -Ctau)/Ctau

Tmin

T_min

TMIN

time

Time of minimum concentration sampled during a dosing interval.

Cmin

C_min

CMIN

amount/volume

Minimum observed concentration between dose time and dose time + Tau.

Cmax

C_max or C_{max, SS}

CMAX

amount/volume

Maximum observed concentration between dose time and dose time + Tau.

MRTINF_obs

MRT_0-inf or MRT_{0-inf, SS}

MRTIVIFO or MRTEVIFO

time

Mean Residence Time extrapolated to infinity using predicted Clast, calculated using AUC_TAU.

T0

T₀

time

Time of the last administered dose (assumed to be zero unless
otherwise specified).

Dose

Dose

–

amount

Amount of the dose

N_Samples

Number of samples

–

unitless

Number of samples in the individuals.

Tlag

T_lag

TLAG

time

Midpoint prior to the first measurable (non-zero) rate.

Tmax_Rate

T_max

ERTMAX

time

Midpoint of collection interval associated with the maximum observed excretion rate.

Max_Rate

Rate_max

ERMAX

amount/time

Maximum observed excretion rate.

Mid_Pt_last

Last midpoint

ERTLST

time

Midpoint of collection interval associated with Rate_last.

Rate_last

Rate_last

ERLST

amount/time

Last measurable (positive) rate.

AURC_last

AURC_0-tlast

AURCLST

amount

Area under the urinary excretion rate curve from time 0 to the last
measurable rate.

AURC_last_D

AURC_0-tlast /Dose

AURCLSTD

unitless

The area under the urinary excretion rate curve (AURC) from time zero to the last measurable rate, divided by the dose.

Vol_UR

Sum of urine volume

VOLPK

volume

Sum of Urine Volumes

Amount_Recovered

Amount recovered

amount

Cumulative amount eliminated.

Percent_Recovered

% recovered

%

100*Amount_Recovered/Dose

AURC_all

AURC_all

AURCALL

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

AURC_0-inf

AURCIFO

amount

Area under the urinary excretion rate curve extrapolated to infinity, based on the last observed excretion rate.

AURC_PerCentExtrap_obs

% extrapolated AURC

AURCPEO

%

Percent of AURC_INF_obs that is extrapolated

AURC_INF_pred

AURC_{0-inf, pred}

AURCIFP

amount

Area under the urinary excretion rate curve extrapolated to infinity, based on the last predicted excretion rate.

AURC_PerCentExtrap_pred

% extrapolated AURC_pred

AURCPEP

%

Percent of AURC_INF_pred that is extrapolated

AURC_T1_T2

AURC_t1-t2

AURCINT

amount

The area under the urinary excretion rate curve (AURC) over the interval from T1 to T2.

AURC_T1_T2_D

AURC_t1-t2/Dose

AURCINTD

unitless

The area under the urinary excretion rate curve (AURC) over the interval from T1 to T2 divided by Dose

Rate_last_pred

Rate_{last, pred}

–

amount/time

The values alpha and Lambda_z are those values found during the regression
for lambda_z

SE_Cmax

SE_Cmax

amount/volume

Sample standard error of the concentration values at Tmax (standard deviation of the y-values at time Tmax divided by the square root of the number of observations at Tmax)

SE_AUClast

SE_AUClast

time⋅amount/volume

with

and

where:

• = time of last measurable (positive) mean concentration

• = number of individuals sampled at both times i and j

• = number of individuals sampled at time i

• = sample variance of concentrations at time i

• = sample covariance between concentrations and for all individuals k that are sampled at both times i and j

SE_AUCall

SE_AUCall

time⋅amount/volume

Same as SE_AUClast with m = last observation time

SE_Max_Rate

SE_{Max_Rate}

amount/time

Same as SE_Cmax with excretion rates

SE_AURC_last

SE_{AURC_last}

amount

Same as SE_AUClast with excretion rates

SE_AURC_all

SE_{AURC_all}

amount

Same as SE_AUCall with excretion rates