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πŸ’‰πŸ’‰ IV Bolus Steady State ​

For IV Bolus at steady state, the following parameters are calculated as described. 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 nameParameter code in outputDescription of calculation
AUC all linear C0AUC_all_lin_C0Sum of partial AUC values for all time points including C0 using the linear method
AUC all linear C0/DoseAUC_all_lin_C0_DAUC_all_lin_C0Dose
AUC all linlog C0AUC_all_log_C0Sum of partial AUC values for all time points including C0 using the linear up log down method
AUC all linlog C0/DoseAUC_all_log_C0_DAUC_all_log_C0Dose
AUC last linear C0AUC_last_lin_C0Sum of partial AUC values from time of dose administration (C0) through TLAST using the linear method
AUC last linear C0/DoseAUC_last_lin_C0_DAUC_last_lin_C0Dose
AUC last linlog C0AUC_last_log_C0Sum of partial AUC values from time of dose administration (C0) through TLAST using the linear up log down method
AUC last linlog C0/DoseAUC_last_log_C0_DAUC_last_log_C0Dose
AUMC last linear C0AUMC_last_lin_C0Sum of partial AUMC values from time of dose administration (C0) through TLAST using the linear methd
AUMC last linlog C0AUMC_last_log_C0Sum of partial AUMC values from time of dose administration (C0) through TLAST using the linear up log down methd
C0C0Log-linear extrapolation back to time of dose administration using the first 2 measured concentration time point.
Last measurable concentrationClastAnalyzed concentration value greater than zero with the largest associated time value.
Maximum concentrationCmaxMaximum concentration value in the analyzed concentration column.
Minimum concentrationCminMinimum concentration value in the analyzed concentration column.
DoseDoseDose amount
Time of DoseDose_timeTime of dose administration
MRT last linear C0MRT_last_lin_C0AUMC_last_lin_C0AUC_last_lin_C0
MRT last linlog C0MRT_last_lin_C0AUMC_last_log_C0AUC_last_log_C0
Number of BLQ samplesN_blqTotal number of observed concentrations reported as "BLQ"
Number of missing samplesN_missTotal number of observed concentrations reported as "Missing"
Number of samplesN_sampTotal number of records in the observed concentration column. Observations that are
SwingSwing(Cmaxβˆ’Cmin)Cmin Reported as missing if Cmin = 0.
Time of ClastTlastValue in the time column the corresponds to Clast.
Time of CmaxTmaxValue 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 CminTminValue 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 interavalend_intervalTime of the end of the dosing interval
Partial AUC from C0 linearpAUC_C0_linPartial area under the curve from C0 to the first measured timepoint using the linear method
Partial AUC from C0 linlogpAUC_C0_logPartial area under the cuver from C0 to the first measured timepoint using the linear up log down methd
TautauDosing interval

Parameters that depend on a terminal slope ​

Parameter nameParameter code in outputDescription of calculation
Percent AUC extrapolated to C0 linearAUC_extrap_C0_lin100βˆ—[pAUC_C0_linAUC_inf_lin_C0]
Percent AUC extrapolated to C0 linlogAUC_extrap_C0_log100βˆ—[pAUC_C0_logAUC_inf_log_C0]
AUC Tau linear C0AUC_tau_lin_C0Sum of partial AUC values from time of dose administration (C0) through end_interval using the linear method
AUC Tau linear C0/DoseAUC_tau_lin_C0_DAUC_tau_lin_C0Dose
Percent extrapolated AUC Tau linear C0AUC_tau_lin_C0_extrap100βˆ—[AUC_tau_lin_C0βˆ’AUC_last_lin_C0AUC_tau_lin_C0]; otherwise 0.
AUC Tau linlog C0AUC_tau_log_C0Sum of partial AUC values from time of dose administration (C0) through end_interval using the linear up log down method
AUC Tau linlog C0/DoseAUC_tau_log_C0_DAUC_tau_log_C0Dose
Percent extrapolated AUC Tau linlog C0AUC_tau_log_C0_extrap100βˆ—[AUC_tau_log_C0βˆ’AUC_last_log_C0AUC_tau_log_C0]; otherwise 0.
AUMC Tau linear C0AUMC_tau_lin_C0Sum of partial AUMC values from time of dose administration (C0) through end_interval using the linear methd
AUMC Tau linlog C0AUMC_tau_log_C0Sum of partial AUMC values from time of dose administration (C0) through end_interval using the linear up log down methd
Accumulation indexAcc_index1(1βˆ’eβˆ’kelβˆ—Tau)
CLss linearCLss_linDoseAUC_tau_lin_C0
CLss linlogCLss_logDoseAUC_tau_log_C0
Average concentration linearCavg_linAUC_tau_lin_C0Tau
Average concentration linlogCavg_logAUC_tau_log_C0Tau
Trough concentrationCtauConcentration 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 linearFluct_lin100βˆ—(Cmaxβˆ’Cmin)Cavg_lin
Fluctuation linlogFluct_log100βˆ—(Cmaxβˆ’Cmin)Cavg_log
Fluctuation Tau linearFluct_tau_lin100βˆ—(Cmaxβˆ’Ctau)Cavg_lin
Fluctuation Tau linlogFluct_tau_log100βˆ—(Cmaxβˆ’Ctau)Cavg_log
MRT linearMRT_linAUMC_tau_lin_C0AUC_tau_lin_C0
MRT linlogMRT_logAUMC_tau_log_C0AUC_tau_log_C0
Swing with CtauSwing_Tau(Cmaxβˆ’Ctau)Ctau Reported as missing if Ctau = 0.
Vss linearVss_lin_C0MRT_lin_C0βˆ—CL_lin_C0
Vss linlogVss_log_C0MRT_log_C0βˆ—CL_log_C0
Vz linearVz_lin_C0Dosekelβˆ—AUC_inf_lin_C0
Vz linlogVz_log_C0Dosekelβˆ—AUC_inf_log_C0
Terminal slope groupgroupGroup 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 interceptinterceptIntercept of linear regression.
Terminal slopekelNegative of estimated slope by linear regression of the natural log-transformed analyzed concentrations and the time of each observation.
Terminal slope adjusted r-squaredkel_adjr21βˆ’(1βˆ’kel_r2)βˆ—[kel_nβˆ’1kel_nβˆ’2]
Terminal slope lower time pointkel_lowSmallest time value used to calculate the terminal slope.
Number of data points in terminal slope calculationkel_nNumber of samples included in teh terminal slope calculation.
Terminal slope r-squaredkel_r2r2 value from terminal slope linear regression.
Terminal slope spankel_spankel_upperβˆ’kel_lowkel_thalf
Terminal half lifekel_thalfln(2)kel
Terminal slope upper time pointkel_upperLargest time value used to calculate the terminal slope.