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

Motivation for ggtibble | Introduction | Typical use | Shorter syntax via the ggtibble chunk option | Footnotes and labels

Quarto + Typst reports | Rendering backends | Topic-grouped listings ("typst" backend)

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

General | Specific Drugs | DDMoRe

Introduction to nlmixr2targets | Initial conditions | Running one model with one dataset (tar_nlmixr()) | Running multiple models with one dataset (tar_nlmixr_multimodel()) | Model piping for multiple models estimated with one dataset | Continuing the pipeline when a model fails | What nlmixr2targets passes to nlmixr2est::nlmixr() -- and what it omits | table (passed, but only when you change it) | ... -- nothing to pass | save -- the targets store already does this | envir -- explicitly omitted

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

What triggers a re-fit? | Examples of common edits | Inspecting and pruning the indirect cache | tar_outdated() is a quick way to preview what would rerun

Why a dedicated multimodel factory? | Minimal comparison plan | Extracting parameter estimates across models | Within-list piping for nested edits | Tips for large model libraries

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

One data frame | Several sheets | What is written | Everything else | Reading it back

A chart | Naming a range | Styling | Axes | The parts of a series | The chart as a whole | A chart on a sheet of its own | Images

Formatting --- vignette | Cell content --- vignette | Worksheet features --- vignette | Printing and the sheet view --- vignette | Charts --- vignette | An image --- vignette | The workbook --- vignette | The second workbook: an embedded image | What was written

Building a format | Applying it to cells | Applying it to columns and rows | Where a format comes from | Conditional formatting | Scales, bars and icons | What is elsewhere

What a cell can hold | Formulas | Hyperlinks | Comments | Rich strings | Mixed columns | Data validation | Autofilters | Worksheet tables | Merged cells | Elsewhere

The sheet | Grouping and outlines | Protection | Silencing Excel's error indicators | The tab strip and the opening view | Printing | The workbook | Memory | Elsewhere

What's implemented | A quick visual comparison | When to use which | Small isolated blobs | Medial axis transform | Distance transform | Inputs and outputs | Performance | References | Thinning | Survey | Medial axis and distance transform

Scope | 1. Edge handling: shapes that touch the frame | 2. Connectivity: thin strokes must not fragment | 3. Distance transform with no background pixel | 4. Invalid input fails loudly | Summary | References

Two forms accepted inside nlmixr2targets | What tar_nlmixr() does behind the scenes | Pipe forms | Known limitation: env functions never routed through tar_nlmixr() | Summary

Reference | EQUIL-2 | Note on phosphate and sulfate units (issue #2) | V1 vs V5 differences (informational)

Reference | How V1 differs from V5 | Quirks preserved by the R port | Numerical verification against the V1 VBA module | EQUIL-2 V1 source

Model library conventions within nlmixr2lib | Compartment naming | Estimated parameter naming | Parameter naming | Multi-component clearance | Parent drug + metabolite parameters | Parameter transforms | Random effects | Covariate effects | Drug effects | Model files

Overview | Population and units | Source trace | Typical-value simulations | Single-dose profiles (100 mg SC) | Target and complex trajectories (1-cmt models) | Repeated SC dosing — drug-concentration difference across structures | Regime-convergence check | Assumptions and deviations

Create your dataset | Create your model | Fit the model | Simulate your data | Summarize the simulations

Model and source | Population | Source trace | Virtual cohort | Simulation | Replicate published figures | Figure 1 / 3 — typical IV vs SC profiles | VPC-style percentile bands | PKNCA validation | Comparison against published NCA | Assumptions and deviations

What is MedDRA? | MedDRA Distribution File Structure | Reading MedDRA Data | Joining into a Single Data Frame | Common Use Cases | Filter by System Organ Class | Find all LLTs for a Preferred Term | Keep only current LLTs | Check the MedDRA version | Working with SMQ Data

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