The following page describes all the parameters computed by the non compartmental analysis. Parameter names are fixed and cannot be changed.
- Parameters related to \(\lambda_z\)
- Parameters related to plasma/blood measurements
- Parameters related to plasma/blood measurements specific to steady state dosing regimen
- Parameters related to urine measurements
- Parameters related to sparse NCA
- Parameter renamings
- Custom (user-defined) NCA parameters
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 | 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. |
| 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 (area under a plot of the product of concentration and time versus time) 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_PerCentExtrap_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_PerCentBack_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_PerCentExtrap_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 |
| 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 intravascular] 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_PerCentExtrap_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_PerCentBack_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_PerCentExtrap_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 | CTAU | Conc Trough | 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 | CTROUGH | Conc Trough | amount/volume | Concentration at end of dosing interval. If the observed concentration does not exist, the value is NaN. |
| 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_PerCentExtrap | – | – | % |
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 |
| FluctuationPerCent | FLUCP | Fluctuation% | % | The difference between Cmin and Cmax standardized to Cavg, between dose time and Tau. Fluctuation% = 100.0* (Cmax -Cmin)/Cavg |
| FluctuationPerCent_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_PerCentExtrap_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_PerCentExtrap_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. |
| AURC_lower_upper_D | AURCINTD | AURC from T1 to T2 Norm by Dose | no unit | The area under the urinary excretion rate curve (AURC) over the interval from T1 to T2 divided by Dose |
| Rate_last_pred | – | – | amount/time | The values alpha and Lambda_z are those values found during the regression for lambda_z |
Parameters related to sparse NCA
| Name | UNITS | DESCRIPTION |
|---|---|---|
| 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 | time.amount/volume | SE_AUClast = \(\sqrt{Var(\hat{AUC})} = \sqrt{\sum_{i=0}^{m} \frac{w_i^2s_i^2}{n_i}+2 \sum_{i<j} \frac{w_i w_j n_{ij} s_{ij}}{n_i n_j}}\)with \( w_{i} = \begin{cases} \frac{t_1-t_0}{2}, & \text{if i=0}\\ \frac{t_{i+1}-t_{i-1}}{2}, & \text{if i=1, …, m}\\ \frac{t_m-t_{m-1}}{2}, & \text{if i=m} \end{cases} \) and \( s_{ij} = \sum_{k=1}^{n_{ij}} \frac{(C_{ik}-\bar{C_i})(C_{jk}-\bar{C_j})}{(n_{ij}-1)+(1-\frac{n_{ij}}{n_i})(1-\frac{n_{ij}}{n_j})}\) where:
|
| SE_AUCall | time.amount/volume | Same as SE_AUClast with m = last observation time |
| SE_Max_Rate | amount/time | Same as SE_Cmax with excretion rates |
| SE_AURC_last | amount | Same as SE_AUClast with excretion rates |
| SE_AURC_all | amount | Same as SE_AUCall with excretion rates |
SE_AUClast, SE_AUCall, SE_AURC_last, SE_AURC_all are available only if the integral method is “linear trapezoidal linear” or “linear trapezoidal linear/log” (because the formula is based on linear calculation of AUC).
Parameter renamings
Starting from the 2023 version of MonolixSuite, default parameter names used in results tables and plots in the graphical user interface and reports do not match the names present in the Name column of the tables above. The names that are used can be customized in the NCA parameters renamings section of Preferences. The section contains two columns:
- Parameter – this column contains parameter names from the tables above,
- Alias – this column contains parameter names used in the interface and the values in cells can be changed.
The Alias column is prefilled with default aliases. By clicking on an alias, PKanalix allows users to input characters. There are several options present, when in the input mode:
- Undo
– reverse the last action, - Redo
– redo an undone action, - Subscript
– formats selected text and subsequently entered characters as subscript, - Superscript
– formats selected text and subsequently entered characters as superscript, - CF
– clears formatting of a selected text, - Cancel
– cancels the changes and restores the alias, - Accept
– accepts the changes (changes can be accepted by clicking anywhere in the interface as well).
