The Options tab allows selection of the NCA model and setting options for that model.
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Use the Model Type menu to select the NCA model type (i.e., whether the input data are from plasma measurements (Plasma (200-202)), urine measurements (Urine (210-212)), or drug effect measurements (Drug Effect (220)).
Check the Sparse box to use analysis methods for sparse datasets.
See the “Sparse sampling calculation” section for more information on using sparse datasets with NCA models.
Use the Weighting menu to select the regression that estimates Lambda Z or slopes. Select User Defined, Uniform, 1/Y, or 1/(Y*Y).
Note: The relative proportions of the weights are important, not the weights themselves. See the “Weighting” section for more on weighting schemes.
Rules for using the Weighting menu:
If User Defined is selected, enter an Observed to Power N value. The value of N must be typed in the Weighting text field.
Sparse data requires Uniform weighting.
When a log-linear fit is done (Uniform weighting for Lambda Z), then the fit is implicitly using a weighting approximately equal to 1/Yhat2.
Note: If 1/Y and the Linear Log Trapezoidal calculation method are selected, one might assume that the weighting scheme is 1/LogY, rather than 1/Y. This is not the case, however, since concentrations between zero and one would have negative weights and could not be included in the analysis.
Use the Titles text box to type a title for the analysis. The title is displayed at the top of each page in the Core Output and can include up to 5 lines of text.
Select a method for calculating the area under the curve from the Calculation Method menu.
The chosen method applies to all AUC, AUMC, and partial area computations. All methods reduce to the log trapezoidal rule, the linear trapezoidal rule, or both. The methods differ based on when the rules are applied. See the “Partial area calculation” section for descriptive equations of the calculation methods. Select from:
Linear Log Trapezoidal. This method uses the linear trapezoidal rule up to Cmax and then the log trapezoidal rule for the remainder of the curve, to compute AUCs. Points for partial areas are inserted using the logarithmic interpolation rule after Cmax, or after C0 for IV bolus, if C0 > Cmax. Otherwise, the linear trapezoidal rule is used. If Cmax is not unique, then the first maximum is used.
Linear Trapezoidal Linear Interpolation. This is the default method and recommended for Drug Effect Data (220). It uses the linear trapezoidal rule, which is applied to each pair of consecutive points in the dataset that have non-missing values, and sums up these areas to compute AUCs. If a partial area is selected that has an endpoint that is not in the dataset, then the linear interpolation rule is used to insert a concentration value for that endpoint.
Linear Up Log Down. The linear trapezoidal rule is used to compute AUCs any time that the concentration data is increasing, the logarithmic trapezoidal rule is used any time that the concentration data is decreasing. Points for partial areas are inserted using the linear interpolation rule if the surrounding points show that concentration is increasing, and the logarithmic interpolation rule if the concentration is decreasing.
Linear Trapezoidal Linear/Log Interpolation. This method is the same as Linear Trapezoidal Linear Interpolation except when a partial area is selected that has an endpoint that is not in the dataset. In that case, the logarithmic interpolation rule is used to insert points after Cmax, or after C0 for IV bolus, if C0 > Cmax. Otherwise, the linear interpolation rule is used. If Cmax is not unique, then the first maximum is used.
Note: The Linear Log Trapezoidal, the Linear Up Log Down, and the Linear Trapezoidal Linear/Log Interpolation methods all apply the same exceptions in area calculation and interpolation. If a Y value (concentration, rate, or effect) is less than or equal to zero, Phoenix defaults to the linear trapezoidal or linear interpolation rule for that point. If adjacent Y values are equal to each other, Phoenix defaults to the linear trapezoidal or linear interpolation rule.
Check the Page Breaks box to include page breaks in the ASCII text output.
Check the Intermediate Output box to add to the text Core Output the values of each iteration during estimation of Lambda Z and for each of the sub-areas in partial area computations.
Check the Disable Curve Stripping box to turn off Lambda Z or slope estimation for all profiles. When this option is selected Lambda Z or slopes are not estimated, parameters that are extrapolated to infinity are not calculated, and the Rules tab is disabled.
Or
To disable curve stripping for one or more individual profiles:
Select Slopes in the Setup tab.
Enter a start time that is greater than the last time point in a given profile and an end time greater than the start time.
Note: Dose Options are not available for the Drug Effect (220) model.
Use the Type menu to select the dosing route.
Dose type selections determine two things: specific model type and columns available in the Dosing panel. Select Extravascular, IV Bolus, IV Infusion, or Dosing Defined.
Set the dosing unit by clicking the Units Builder - Dose […] button or typing the dosing unit into the Unit text field.
Only applicable when an internal worksheet is being used for the Dosing data. See the “Using the Units Builder” section in the Common Tasks documentation for more details.
Press Preview to see a preview of dose option selections in a separate window.
Press OK to close the preview window.
Use the Normalization menu to select the appropriate factor if the dose amount is normalized by subject body weight or body mass index.
Select None, kg. g, mg, m**2, or 1.73 m**2.
If doses are in milligrams per kilogram of body weight, select mg as the dosing unit and kg as the dose normalization.
The Normalization menu affects the output parameter units. For example, if dose volume is in liters, selecting kg as the dose normalization changes the units to L/kg. Dose normalization affects units for all volume and clearance parameters in NCA models, as well as AUC/D in NCA plasma models, and Percent_Recovered in NCA urine models.
Enter the Max # of Profiles for User Range Selections in the field (default is 100).
If the number of profiles exceeds this value, then the selection of slopes will be disabled and the engine will calculate the slopes using the Best Fit method. Selecting the Slopes Selector worksheet or Slopes worksheet will display a message notifying that the limit has been exceeded and the Best Fit method will be used for all profiles.
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