PK_Parameters

PK Parameters

Using AutoPilot Toolkit, the administrator can select which output (tables, graphs, and appendices) is available for selection in the Automation and Comparison interfaces. In addition, an administrator can filter which PK parameters are available and provide defaults for each table, graph, or text type if they are displayed. The “PK automation parameters” section presents the full list of PK parameters that administrators can include in the PK tables and graphs from PK Automation projects. The “PK comparison parameters” section presents the PK parameters that are included in the output from PK Comparison projects.

PK automation parameters

The following table lists the available PK parameters that can be selected for output from automation projects and their treatment in the default output, including the tables PKParameter_A, PKParameter_B, Intext_PK_Parameter_I, Urine_PK_Parameter, Urine_Intext_PK_Parameter, PK_Ratios, Urine_PK_Ratios, PK_Stats, Urine_PK_Stats, and Lambda_Z. The list of available parameters varies by NCA model and whether the study contains single-dose (SD) or multiple-dose (MD) data.

Note: For the NCA Model 220, Lambda Z values calculated in Phoenix may differ slightly from results calculated using WinNonlin version 5.x and earlier due to the default setting for the slope being changed from Time Ranges to Best Fit.

Definitions for terms appearing in the table:

WNL Name: Name (column header) provided by NCA model output.

Def Disp Name: Default name displayed in the final output (tables, graphs, and text).

Mod: Parameter is available for a specific NCA Model (e.g., 200 Ext) and regimen (Single-Dose (1D) or Multiple-Dose (MD)).

Def Table: Parameter displays in a specific table by default (LZ = Lambda Z).

Def Graph: Parameter is used for the creation of PK parameter graphs by default.

Ratios/Stats: Parameter displays in the PK Ratios and PK Stats tables by default.

Div/Sub: Parameter is set to show differences in the PK Ratios table based on subtraction (e.g., Trt 2 – Trt 1) or division (Trt 2/Trt 1).

Def Precision: Default precision regarding the type (significant figures or decimal places) and value (e.g., 0) to display in tables.

Normalization: If parameter can have normalization applied to it.

Def Summary / Error: Default summary (e.g. mean) and error term (e.g., SD) per PK parameter for graphs.

Cfg: Default values are configurable in the Administrator Module.

WNL Name [Def Display] (Cfg)	Mod 200 (Ext)		Mod 201 (IV bolus)		Mod 202 (IV infusion)		Mod 210–212 (urine)	Def Table (Cfg)	Def Graph (Cfg)	Ratio/Stats (Cfg)	Div/Sub	Def Precision Type/Value (Cfg)	Normalization	Def Summary / Error (Cfg)
	1D	MD	1D	MD	1D	MD	1D MD
Accumulation_Index [Accumulation]		X		X		X		N	N	N	S	dec/0	N	Mean/SD
Amount_Recovered [Ae]							X	Urine Intext	Y	Y	D	sig/3	Y	Mean/SD
AUC_%Back_Ext_obs [AUC % Back Extrap]			X	X				N	N	N	S	dec/0	N	Mean/SD
AUC_%Back_Ext_pred [AUC % Back Extrap]			X	X				N	N	N	S	dec/0	N	Mean/SD
AUC_%Extrap_obs [AUC % Extrap]	X	X	X	X	X	X		PKA	N	N	S	dec/0	N	Mean/SD
AUC_%Extrap_pred [AUC % Extrap]	X	X	X	X	X	X		N	N	N	S	dec/0	N	Mean/SD
AUC_TAU [AUC_t]		X		X		X		PKA, Intext	Y	Y	D	sig/3	Y	Mean/SD
AUCall [AUC_all]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
AUCINF_D_obs [AUC_¥/D]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
AUCINF_D_pred [AUC_¥/D]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
AUCINF_obs [AUC_¥]	X	X	X	X	X	X		PKA, Intext	Y	Y	D	sig/3	Y	Mean/SD
AUCINF_pred [AUC_¥]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
AUClast [AUC_last]	X	X	X	X	X	X		PKA, Intext	Y	Y	D	sig/3	Y	Mean/SD
AUMC_%Extrap_obs [AUMC % Extrap]	X		X		X			N	N	N	S	dec/0	N	Mean/SD
AUMC_%Extrap_pred [AUMC % Extrap]	X		X		X			N	N	N	S	dec/0	N	Mean/SD
AUMC_TAU [AUMC_t]		X		X		X		N	N	N	D	sig/3	Y	Mean/SD
AUMCINF_obs [AUMC_¥]	X		X		X			N	N	N	D	sig/3	Y	Mean/SD
AUMCINF_pred [AUMC_¥]	X		X		X			N	N	N	D	sig/3	Y	Mean/SD
AUMClast [AUMC_last]	X		X		X			N	N	N	D	sig/3	Y	Mean/SD
AURC_%Extrap_obs [AURC % Extrap]							X	N	N	N	S	dec/0	N	Mean/SD
AURC_%Extrap_pred [AURC % Extrap]							X	N	N	N	S	dec/0	N	Med/MinMax Mean/SD
AURC_all [AURC_all]							X	N	N	N	D	sig/3	Y	Mean/SD
AURC_INF_obs [AURC_¥]							X	N	N	N	D	sig/3	Y	Mean/SD
AURC_INF_pred [AURC_¥]							X	N	N	N	D	sig/3	Y	NA
AURC(x-y) [AURC^a]							X	N	N	N	D	sig/3	Y	NA
AURClast [AURC_last]							X	N	N	N	D	sig/3	Y	Mean/SD
C0 [C₀]			X	X				N	N	N	D	sig/3	Y	Mean/SD
Cavg [C_avg]		X		X		X		PKB	Y	N	D	sig/3	Y	Mean/SD
Cl_F_obs [CL/F]	X							PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Cl_F_pred [CL/F]	X							N	N	N	D	sig/3	Y	Mean/SD
Cl_obs [CL]			X		X			PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Cl_pred [CL]			X		X			N	N	N	D	sig/3	Y	Mean/SD
Clast [C_last]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
CLss [CL_ss]				X		X		PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
CLss_F [CL_ss/F]		X						PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Cmax [C_max]	X	X	X	X	X	X		PKA, Intext	Y	Y	D	sig/3	Y	Mean/SD
Cmax_D [C_max/Dose]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
Cmin [C_min]		X		X		X		N	N	N	D	sig/3	Y	Mean/SD
Corr_XY [Correlation]	X	X	X	X	X	X		N	N	N	S	sig/3	N	Med/MinMax
Fluctuation% [Fluctuation %]		X		X		X		PKB, Intext	Y	N	S	dec/0	N	Mean/SD
HL_Lambda_z [t_1/2]	X	X	X	X	X	X		PKB, Intext	Y	N	D	dec/2	Y	Mean/SD
Lambda_z [l_z]	X	X	X	X	X	X		LZ	Y	N	D	sig/3	N	Mean/SD
Lambda_z_lower [l_{z Lower}]	X	X	X	X	X	X		LZ	N	N	S	dec/2	N	Med/MinMax
Lambda_z_upper [l_{z Upper}]	X	X	X	X	X	X		LZ	N	N	S	dec/2	N	Med/MinMax
Max_Rate [Max Rate]							X	N	N	N	S	sig/3	Y	Med/MinMax
Mid_Pt_last [Midpoint]							X	N	N	N	S	dec/2	N	Med/MinMax
MRTINF_obs [MRT_¥]	X	X	X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
MRTINF_pred [MRT_¥]	X	X	X	X	X	X		N	N	N		sig/3	Y	Mean/SD
MRTlast [MRT_last]	X		X		X			N	N	N	D	sig/3	Y	Mean/SD
No_points_lambda_z [Number of Points]	X	X	X	X	X	X		LZ	N	N	S	dec/0	N	Med/MinMax
Partial_Area [AUC ^a]	X	X	X	X	X	X		PKB	Y	N	D	sig/3	Y	Mean/SD
Percent_Recovered [fe]							X	Urine Intext	Y	Y	S	dec/0	Y	Mean/SD
Rate_last [Last Rate]							X	N	N	N	S	sig/3	Y	Med/MinMax
Rsq [R²]	X	X	X	X	X	X		N	N	N	S	sig/3	N	Med/MinMax
Rsq_adjusted [R² Adjusted]	X	X	X	X	X	X		X	N	N	S	sig/3	N	Med/MinMax
Tlag [T_lag]	X	X						PKB	N	N	S	dec/2	N	Med/MinMax
Tlast [T_last]	X	X	X	X	X	X		N	N	N	S	dec/2	N	Med/MinMax
Tmax [T_max]	X	X	X	X	X	X		PKA, Intext	Y	N	S	dec/2	N	Med/MinMax
Tmax_Rate [T_max Rate]							X	N	N	N	S	dec/2	N	Med/MinMax
Tmin [T_min]		X		X		X		N	N	N	S	dec/2	N	Med/MinMax
Vol_UR [Volume]							X	N	N	N	D	dec/0	Y	Mean/SD
Vss_obs [V_ss]			X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
Vss_pred [V_ss]			X	X	X	X		N	N	N	D	sig/3	Y	Mean/SD
Vss/F_obs [V_ss/F]	X	X						N	N	N	D	sig/3	Y	NA
Vss/F_pred [V_ss/F]	X	X						N	N	N	D	sig/3	Y	NA
Vz [V_z]				X		X		PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Vz_F [V_z/F]		X						PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Vz_F_obs [V_z/F]	X							PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Vz_F_pred [V_z/F]	X							N	N	N	D	sig/3	Y	Mean/SD
Vz_obs [V_z]			X		X			PKB, Intext	Y	N	D	sig/3	Y	Mean/SD
Vz_pred [V_z]			X		X			N	N	N	D	sig/3	Y	Mean/SD

a.The display name is amended by the time period for the AUC calculation, for example, AUC0-24.

PK comparison parameters

PK Comparison projects calculate the following additional PK parameters, which can be selected for inclusion for a given comparison run. This includes analyte, accumulation, absolute bioavailability, and renal clearance comparisons.

(In the following table “Accum” = Accumulation, “AbBio” = Absolute Bioavailability, “RenCl” = Renal Clearance.)

PK Parameter	Equation	Precision Type /Default	Comparison Type
PK Parameter	Equation	Precision Type /Default	Plasma	Trough	Accum	AbBio	RenCl
CLr	Ae(URN)/AUClast	Sig/3					X
DoseExt	NA	Dec/0				X	X
DoseIV	NA	Dec/0				X	X
Fabs	AUCinf(PO)Dose(IV)/AUCnf(IV)Dose(PO)*100	Dec/0				X	X
LI	AUCtau(MD)/AUCinf(SD)	Dec/3			X
RA^{^a}	AUCtau(MD)/AUCtau(SD)	Dec/3			X

a.RA is calculated from the equation RA=AUCtau(MD)/AUCtau(SD). Since Phoenix does not calculate AUCtau for SD, a Partial AUC for the SD model that is equal to the interval of the tau must be created. When RA is calculated, AutoPilot Toolkit checks that the parameter Tlast for MD is the same as the interval for the Partial Area set up in the SD model (e.g., tlast=AUC Partial Interval). If these are the same, RA is calculated using the above equation. If these values do not match, RA is calculated using the equation, RA=AUCtau (MD)/AUClast (SD).