Package: PKNCA 0.12.1.9002

Summary and recommendations | Introduction | The sparse AUC to the last measurement | Extrapolation to infinity (Yuan 1993) | IV bolus: the back-extrapolated C0 | The uncertainty of lambda.z (delta method) | Degrees of freedom | An alternative: lambda.z from the individual samples | Simulation-estimation study | Design | Results: coverage of the AUC to infinity | Results: coverage of the AUMC to infinity | Results: the bootstrap | Results: the bootstrap with more animals at each time | Results: the Tobit half-life with BLQ samples | Results: accuracy of the point estimates | Findings | Arithmetic or geometric mean profiles | Calculating it with PKNCA | Discussion | References

Sparse NCA Setup | Data Setup Note | How Subjects Are Grouped for Sparse Calculations | Calculate! | Results | Sparse AUC, AUMC, and Derived Parameters | Bootstrap | Deprecated Parameter Names | Notes on Sparse Calculation Behavior | Degrees of freedom with multiple samples per subject | More than half of the measurements below the limit of quantification | Only the linear trapezoidal method is supported

Introduction | Group Matching | Selecting the Subjects for an Interval | Intervals | Automatic Selection of Intervals | Finding the Dosing Interval | To Infinity | Multiple Intervals | Overlapping Intervals and Different Calculations by Interval | Intervals with Duration | Multiple-Dose MRT and Vss | Intravenous Infusions | Parameters Available for Calculation in an Interval

Writing the Parameter Function | Requirements | Best Practices | Tell PKNCA about the Parameter | Passing a Constant with formalsmap | Parameters That Need Another Interval | Tell PKNCA How to Summarize the Parameter | Putting It Together

Introduction | Setup | Modifying Results | Exclusion of Select Results | Exclusion Functions | Missing Samples and $T_{max}$ Coverage | Excluding Specific Results | Multiple Exclusions | Normalizing Results | Example: Normalize by a column in the concentration data | Doing custom normalizations | Extracting Results | Summary Results | Listing of Results | Concentrations Used for Half-Life Estimation | The Half-Life Fit | Concentrations Along the Half-Life Fit

Introduction | Curve Stripping Method | Select the Points | Select the Best Fit | Example | Manual Point Selection | Choosing a Point Selection Method | Column Requirements | Exclusion of Specific Points with Curve Stripping | Specification of the Exact Points for Analysis

Introduction to PKNCA | Dataset Basics | NCA Data are Not Tidy as a Single Dataset | Dataset Basics: What columns are needed? | Dataset Basics: Example interval data | PKNCA Functions | What functions are the most used? | How do I do a simple calculation? all steps | How do I do a simple calculation? Concentration data | How do I do a simple calculation? Dose data | How do I do a simple calculation? Calculate results | How do I do a simple calculation? Get results | How do I do a simple calculation? Get summary results | How do I do a simple calculation? Get individual results | PKNCA datasets | How does PKNCA think about data? | What is an "interval" and how is it different than a "group"? | Reporting | Best practices for Data -> PKNCA -> knitr/Quarto | Graphics are intentionally not part of PKNCA, but there are some tricks that can help... | Validation of PKNCA | More information

Introduction | Examples of each way to add units | Steps to add units to an NCA analysis from the data | Steps to manually add units to an NCA analysis | Prepare a Unit Assignment and Conversion Table | What happens when units are missing for some parameters? | How do I add different unit conversions for different analytes? | Date and time (POSIXct) input

How the calculation works | Optional packages | Simulating a 2x2 crossover study | Noncompartmental analysis | Bioequivalence assessment | Interpreting the results | Reference scaling and regulatory frameworks | A replicate-design study | Comparing frameworks side by side | Unequal variances, covariates, and descriptive comparisons | Reporting checklist

Preparation | AUC to the Last Value Above the Limit of Quantification (AUC~last~) | AUC~all~ | AUC to Infinity (AUC~$\infty$~) | Partial AUCs

Introduction to PKNCA and Basics of Its Use | Introduction to PKNCA | Enjoy! | Some NCA Definitions | Dataset Basics | NCA Data are Not Tidy as a Single Dataset | Dataset Basics: Minimum data | Dataset Basics: What columns are needed? | Dataset Basics: Example data | Dataset Basics: Example concentration data | Dataset Basics: Example dosing data | Dataset Basics: Example interval data | Hands-on: First NCA calculation with PKNCA | PKNCA Functions | What functions are the most used? | How do I do a simple calculation? all steps | How do I do a simple calculation? Concentration data | How do I do a simple calculation? Dose data | How do I do a simple calculation? Calculate results | How do I do a simple calculation? Get results | How do I do a simple calculation? Get summary results | How do I do a simple calculation? Get individual results | PKNCA datasets | How does PKNCA think about data? | What is an "interval" and how is it different than a "group"? | Common data management requirements before sending data to PKNCA | Setup your concentration data | Setup your dosing data (if you have it and even if you don't) | Define your intervals | Define your intervals: example | Calculations above the hood | Prepare your data for calculation | Calculate without dosing data | Calculate without dosing data, try 2 | Dosing data helps with interval setup | AUC considerations with PKNCA (1/3) | AUC considerations with PKNCA (2/3) | AUC considerations with PKNCA (3/3) | Hands-on workshop | Steady-state intramuscular administration | Day 2 Start | Control your data | Including and excluding data points | Exclude data points overall | Exclude data points overall | Digression: How is λz automatically calculated? | λz control (manual exclusions and inclusions of data points) | Less-common calculations | Urine calculations | Urine calculations: understanding what is happening and potential hiccups | Calculations below the hood | PKNCA only calculates what is required, not every possible parameter (1 of 2) | PKNCA only calculates what is required, not every possible parameter (2 of 2) | How to select the correct parameters for calculations (aka, why are there r sum(grepl(x=names(PKNCA.options("single.dose.aucs")), pattern="^auc")) types of AUC in PKNCA?) | When are intervals (partly) ignored? | Control your results | Excluding results (Not the best way) | Excluding results (The best way, 1/2) | Excluding results (The best way, 2/2) | NCA-related calculations | Superposition | Time-to-Steady-state calculations | Reporting | Graphics are intentionally not part of PKNCA, but there are some tricks that can help... | Best practices for Data -> PKNCA -> knitr | Units (especially clearance) | Data imputation | IV bolus AUC (need to add C0) | Combined, multi-subject data (e.g. sparse animal sampling) | Limitations | Secondary parameters (e.g. bioavailability and renal clearance) | Validation of PKNCA | Hands-on | Single- and Multiple-dose, single analyte: Setup the underlying datasets | Single- and Multiple-dose, single analyte: Setup the concentration and dose datasets | Single- and Multiple-dose, single analyte: Perform basic analysis | Single- and Multiple-dose, single analyte: Use intervals for fewer subjects | Single- and Multiple-dose, single analyte: Use custom intervals per subjects | Single- and Multiple-dose, parent and metabolite

Comparison to semi-log regression | Automatic point selection | Automatic point selection with semi-log regression | Automatic point selection with Tobit regression | Comparison of Tobit and semi-log regression | Usage | Basic usage: a single subject | Example 1: All observations above the LLOQ | Example 2: BLQ observations before T~last~ | Using the global option | Full NCA workflow with PKNCAdata | Controlling Tobit point selection

What a secondary parameter is | Linking two intervals by hand | Renal clearance, start to finish | The reference interval gains what the link needs | Letting PKNCA find the reference interval | When more than one profile could be the reference | Steering the choice with group_ref | Writing the linkage into the intervals | Bioavailability | Exclusions cross the link | Units that differ between the two profiles | A ratio standardizes to a fraction | A quotient that is not a fraction | Reporting | Limitations | See also

How does imputation occur? | How to select imputation methods to use | Imputation for the full dataset | Imputation by calculation interval | Advanced: Writing your own imputation functions

Quick Start | Data Handling | Options: Make PKNCA Work Your Way | Calculation Options: the PKNCA.options Function | Summarization Options: the PKNCA.set.summary Function | Grouping NCA Data | Selecting Calculation Intervals | Selection of Data Used for Calculation | Automatic Interval Determination | Manual Interval Specification | Keeping a column from intervals | Summarizing results | Updating existing results

Load the data | Merge the Concentration and Dose | Compute the parameters | Multiple Dose Example

Introduction | Methods | Appendix: Complete Methods Table

Example | Data setup | Estimate time to Steady State | Monoexponential | Stepwise Linear | References

Introduction | Summary of Testing | Session Information

Load the data | Compute the Superposition from Single-Dose Data to Steady-State | Nonstandard Superposition Computations | Compute the Superposition from Single-Dose Data to a Specific Dose | Compute the Superposition from Single-Dose Data with >1 Dose Per Interval | Simulate a Different Dose Amount | Show the Curve to Steady-State | Time Point Selection and Addition | Interpolation and Extrapolation Methods

Integration methods for Area Under the Concentration-Time curve (AUC) | Definitions and abbreviations | Description of methods of integrating between two concentrations before T~last~ | Linear up/logarithmic down ("lin up/log down") interpolation | Linear trapezoidal ("linear") interpolation | Linear to T~max~/logarithmic after T~max~ ("lin-log") interpolation | Description of methods of integrating between two concentrations after T~last~ | "AUClast" extrapolation | "AUCall" extrapolation | "AUCinf" extrapolation | Examples

Summary | Options