Sometimes it’s good to have a day off in the middle of the work week. I finished up something that I’ve had on my to-do list for years: a distribution plot for population analysis of Vol dist. The plot compares the 3-sigma normal distribution curve (green line) vs actual data points (red bars). Although it’s helpful to have descriptive statistics, nothing beats a picture:

The population analysis report had to be re-arranged to fit the new plot on the page . I believe it is an easier read now. Here’s a comparison of new vs old:

Other improvements to the population analysis tool include:

• BMI analysis option
• CL vs Kel regression option
• Automatically create/save graphs

While testing all these changes with real-world data I noticed a handful of Vd values in the consult table that were Zero. Further investigation revealed that these were *huge* patients with Vd’s > 100 liters. When I originally set up the APK database format over twenty years ago I did not forsee the U.S. obesity epidemic. Nowadays it is not unusual for us to see patients who are 300, 400, 500+ pounds, a sad commentary on the state of our country’s health. Also, I didn’t realize if the database engine encounters a number exceeding the defined field, it just skips it! It doesn’t flag an error, it just puts in a zero… WTF? Anyway, this update includes a change to the consults table, increasing the width of the Vd field from 4 to 5. This will accommodate patients up to 700 kg. If that limit is exceeded, please stop this planet and let me off.

Enjoy.

APK for Windows version 3.5.16 is available. Highlights include:

• Added a point prediction tool.
• Improved the ‘Outlier’ message dialog.
• Added a goodness-of-fit indicator to the Bayesian results dialog.
• Improved the ‘Non-steady-state’ message dialog.
• Improved the serum level graph print-out.
• Updated the help file.

Point prediction tool
Provides serum level prediction at any point within the dosing regimen. I find this useful for timing off-schedule doses and for evaluating non-steady-state levels.

Improved outlier message
Added detail to the Bayesian outlier message. Here is the old message:

And here is the improved message:

Goodness-of-fit indicator
A goodness-of-fit indicator was added to the Bayesian results dialog. This parameter is used to evaluate the reliability of the serum level analysis. The following parameters are included in the test:

• Initial SS < 5
• Final SS < 0.5
• Final Vd SD < Model Vd SD
• Final Kel SD < Model Kel SD
• Predicted level = Measured level

If all 5 parameters are true, the measurement-to-model fit is excellent; 4/5 is a good fit; 3/5 is a fair fit; less than 3 is a poor fit.

Improved ‘Non-steady-state’ dialog
The previous dialog was wordy and vague:

The new dialog is simpler with clear choices:

Today I finished the latest update of the APK for Windows program to version 3.5.15.

Highlights include:

• Added a “virtual log paper” tool.
• Added automatic peak time calculation based on dist time.
• Changed model editor to prevent name change.
• Fixed gender choice on population analysis.
• Fixed non-steady-state dialog.
• Improved consult print-out: added method used, model selected.
• Updated help file.

What I’m most proud of in this version is the new “virtual log paper” function. So many times over the years I’ve had to bring out the 3-cycle log paper to plot data for an outlier.

FYI, this is the 42nd time the program has been updated since it was first conceived in 1999. The original idea behind the APK program was to strip Kinetics down to one-compartment models only and add support for pediatric dosing. The executable was (and still is) small enough to run off a floppy drive.

But it has grown in complexity over the years. I decided to have some fun comparing code metrics from the original release to this one:

Forms: increased from 20 to 33
Code files: increased from 20 to 44
Functions: increased from 124 to 348
Events: increased from 202 to 2385 (not a typo!)
Lines of code: increased from 10,690 to 67,742.

In addition to the code base, the application includes an exhaustive help file with 81 topics, 85 images, and 14,260 lines of text.

To quote the Dude: “A lot of ins, a lot of outs, a lot of what-have-yous, and, a lot of strands to keep in my head, man. A lot of strands in old Duder’s head.”

So, forgive me if I forget your name next time we meet.

Finished up work on the latest iteration of the new program, Half-life calculator.

Summary of changes:

• Changed serum level entry to a grid.
• Up to 10 level/time pairs can be entered.
• Added logarithmic graph of plot points and regression line
• Added report function
• Added built-in help.
• Added save/load of serum level profiles
• Added toolbar.

Main dialog:

Graph:

Report:

Just wish I could think of a “catchy” name for it 🙂

Finished updating rxkinetics.net this week:

• Updated the help files
• Tweaked TPN screens
• Added aztreonam model per request

I had some time to work on a new project for the UK National Poisons Information Service. A professor there had purchased KinPlot. I sent him a note of thanks, he responding by saying “I thought it would help a clinical pharmacology student calculate a half-life which of course it does not!” After more back and forth I agreed to write a little program to estimate half-life and dose for poisoning cases. Inputs are estimated time of ingestion and 2 to 4 level/date pairs. Option to solve for dose or volume of distribution. The program calculates Kel, half-life, Cp_max, and dose (or Vd) using least squares linear regression. Screen shot:

I will be adding graph and report functionality when I find more time. I am thinking about somehow incorporating this into my pk programs. After 30 years I may be able to finally put away the 3-cycle log paper. But then again, I think I would miss it.