💊💊 Extravascular Steady State

For extravascular administration at steady state, the following parameters are calculated as described. The extravascular route includes oral, topical, sublingual, subcutaneous, intramuscular, rectal, and any other route that is not intravenous. The term steady state means that the rate of input and rate of elimination of the drug are equivalent; however, there is nothing in the data of a single dosing interval that can independently determine if steady state has been achieved. A user must confirm that steady state has been achieved by other methods (e.g. monitoring trough values over several dosing intervals).

Imputations

If the analysis dataset does not include a concentration value at the time of dose administration, a value will be imputed from the dataset. That value will be the minimum observed concentration between the time of dose administration and dose administration plus the dosing interval (Tau). The imputed concentration will be added to the dataset with a time value equal to the time of dose administration. This value is used in all parameter calculations.

If the analysis dataset does not include a concentration value at time Tau, a value will be imputed from the dataset. That value will be extrapolated from the last time point prior to Tau using the terminal elimination rate constant as described in extrapolation methods.

Parameters that do not depend on a terminal slope

Parameter name	Parameter code in output	Description of calculation
AUC all linear	AUC_all_lin	Sum of partial AUC values for all time points using the linear method
AUC all linear/Dose	AUC_all_lin_D	$\frac{AUC\mathrm{\_}all\mathrm{\_}lin}{Dose}$
AUC all linlog	AUC_all_log	Sum of partial AUC values for all time points using the linear up log down method
AUC all linlog/Dose	AUC_all_log_D	$\frac{AUC\mathrm{\_}all\mathrm{\_}log}{Dose}$
AUC last linear	AUC_last_lin	Sum of partial AUC values from time of dose administration through Tlast using the linear method
AUC last linear/Dose	AUC_last_lin_D	$\frac{AUC\mathrm{\_}last\mathrm{\_}lin}{Dose}$
AUC last linlog	AUC_last_log	Sum of partial AUC values from time of dose administration through Tlast using the linear up log down method
AUC last linlog/Dose	AUC_last_log_D	$\frac{AUC\mathrm{\_}last\mathrm{\_}log}{Dose}$
AUMC all linear	AUMC_all_lin	Sum of partial AUMC values for all time points using the linear methd
AUMC all linlog	AUMC_all_log	Sum of partial AUMC values for all time points using the linear up log down methd
AUMC last linear	AUMC_last_lin	Sum of partial AUMC values from time of dose administration through Tlast using the linear methd
AUMC last linlog	AUMC_last_log	Sum of partial AUMC values from time of dose administration through Tlast using the linear up log down methd
Last measurable concentration	Clast	Analyzed concentration value greater than zero with the largest associated time value.
Maximum concentration	Cmax	Maximum concentration value in the analyzed concentration column.
Cmax/Dose	Cmax_D	$\frac{Cmax}{Dose}$
Minimum concentration	Cmin	Minimum concentration value in the analyzed concentration column.
Dose	Dose	Dose amount
Time of Dose	Dose_time	Time of dose administration
Number of BLQ samples	N_blq	Total number of observed concentrations reported as "BLQ"
Number of missing samples	N_miss	Total number of observed concentrations reported as "Missing"
Number of samples	N_samp	Total number of records in the observed concentration column. Observations that are below the limit of quantitation (BLQ) are counted, but missing observations are not counted.
Swing	Swing	$\frac{(Cmax-Cmin)}{Cmin}$ Reported as missing if Cmin = 0.
Time of Clast	Tlast	Value in the time column the corresponds to Clast.
Time of Cmax	Tmax	Value in time column that corresponds to the maximum concentration. If there are two identical values at the maximum concentration, the earliest time is reported.
Time of Cmin	Tmin	Value in time column that corresponds to the minimum concentration. If there are two identical values at the minimum concentration, the earliest time is reported.
End of dosing interaval	end_interval	Time of the end of the dosing interval
Tau	tau	Dosing interval

Parameters that depend on a terminal slope

Parameter name	Parameter code in output	Description of calculation
AUC Tau linear	AUC_tau_lin	Sum of partial AUC values from time of dose administration through end_interval using the linear method
AUC Tau linear/Dose	AUC_tau_lin_D	$\frac{AUC\mathrm{\_}tau\mathrm{\_}lin}{Dose}$
Percent extrapolated AUC Tau linear	AUC_tau_lin_extrap	$100\ast [\frac{AUC\mathrm{\_}tau\mathrm{\_}lin-AUC\mathrm{\_}last\mathrm{\_}lin}{AUC\mathrm{\_}tau\mathrm{\_}lin}]$; otherwise 0.
AUC Tau linlog	AUC_tau_log	Sum of partial AUC values from time of dose administration through end_interval using the linear up log down method
AUC Tau linlog/Dose	AUCINFLOG_D	$\frac{AUC\mathrm{\_}tau\mathrm{\_}log}{Dose}$
Percent extrapolated AUC Tau linlog	AUC_tau_log_extrap	$100\ast [\frac{AUC\mathrm{\_}tau\mathrm{\_}log-AUC\mathrm{\_}last\mathrm{\_}log}{AUC\mathrm{\_}tau\mathrm{\_}log}]$; otherwise 0.
AUMC Tau linear	AUMC_tau_lin	Sum of partial AUMC values from time of dose administration through end_interval using the linear methd
AUMC Tau linlog	AUMC_tau_log	Sum of partial AUMC values from time of dose administration through end_interval using the linear up log down methd
Accumulation index	Acc_index	$\frac{1}{(1-e^{-kel\ast Tau})}$
CLss/F linear	CLss_F_lin	$\frac{Dose}{AUC\mathrm{\_}tau\mathrm{\_}lin}$
CLss/F linlog	CLss_F_log	$\frac{Dose}{AUC\mathrm{\_}tau\mathrm{\_}log}$
Average concentration linear	Cavg_lin	$\frac{AUC\mathrm{\_}tau\mathrm{\_}lin}{Tau}$
Average concentration linlog	Cavg_log	$\frac{AUC\mathrm{\_}tau\mathrm{\_}log}{Tau}$
Trough concentration	Ctau	Concentration at time equal to end_interval. If an observed value is not available, logarithmic extrapolation using Clast and kel is performed. Reported as 0 if there is a BLQ value at time equal to end_interval.
Fluctuation linear	Fluct_lin	$100\ast \frac{(Cmax-Cmin)}{Cavg\mathrm{\_}lin}$
Fluctuation linlog	Fluct_log	$100\ast \frac{(Cmax-Cmin)}{Cavg\mathrm{\_}log}$
Fluctuation Tau linear	Fluct_tau_lin	$100\ast \frac{(Cmax-Ctau)}{Cavg\mathrm{\_}lin}$
Fluctuation Tau linlog	Fluct_tau_log	$100\ast \frac{(Cmax-Ctau)}{Cavg\mathrm{\_}log}$
MRT linear	MRT_lin	$\frac{AUMC\mathrm{\_}tau\mathrm{\_}lin}{AUC\mathrm{\_}tau\mathrm{\_}lin}$
MRT linlog	MRT_log	$\frac{AUMC\mathrm{\_}tau\mathrm{\_}log}{AUC\mathrm{\_}tau\mathrm{\_}log}$
Swing with Ctau	Swing_Tau	$\frac{(Cmax-Ctau)}{Ctau}$ Reported as missing if Ctau = 0.
Vz/F linear	Vz_f_lin	$\frac{Dose}{kel\ast AUC\mathrm{\_}tau\mathrm{\_}lin}$
Vz/F linlog	Vz_f_log	$\frac{Dose}{kel\ast AUC\mathrm{\_}tau\mathrm{\_}log}$
Terminal slope group	group	Group number for each estimated terminal slope. For each profile at least one terminal slope is calculated. All parameters that are dependent on estimation of the terminal slope are also calcualted and given the same group number.
Terminal slope intercept	intercept	Intercept of linear regression.
Terminal slope	kel	Negative of estimated slope by linear regression of the natural log-transformed analyzed concentrations and the time of each observation.
Terminal slope adjusted r-squared	kel_adjr2	$1-(1-kel\mathrm{\_}r2)\ast [\frac{kel\mathrm{\_}n-1}{kel\mathrm{\_}n-2}]$
Terminal slope lower time point	kel_low	Smallest time value used to calculate the terminal slope.
Number of data points in terminal slope calculation	kel_n	Number of samples included in teh terminal slope calculation.
Terminal slope r-squared	kel_r2	r2 value from terminal slope linear regression.
Terminal slope span	kel_span	$\frac{kel\mathrm{\_}upper-kel\mathrm{\_}low}{kel\mathrm{\_}thalf}$
Terminal half life	kel_thalf	$\frac{ln(2)}{kel}$
Terminal slope upper time point	kel_upper	Largest time value used to calculate the terminal slope.