Purchase replacement installation CD here

Vancomycin is a difficult drug to dose because of extreme inter-patient variability of pk parameters. No single model will fit all patient populations.

• Look at the divergent models from the literature

The two models roughly parallel the two divergent dosing methods:

• The Normal or CL model calculates a clearance and was derived from the work of Winter.
• The Outlier or Kel model calculates an elimination rate constant (Kel), and was derived from the works of Matzke.

Patients who may be more appropriately dosed with the outlier model include:

• obese patients (BMI > 30)
• underweight and/or malnourished patients
• nonambulatory patients (likely to have low muscle mass)
• diabetics
• patients with acute or chronic renal failure

Please bear in mind that vancomycin is not a very predictable drug, and these models will not fit all patient populations. It is important to save your data, and to periodically re-analyze your population parameters vs outcome. This is where the population analysis utility included with APK© will allow you to create models fitted to your patient population.

You may analyze a single trough, a single peak, or a random level drawn at any point within the dosing interval by selecting the single point Bayesian method. On the Hand-held versions of APK©, this method is designated by the abbreviation "B".

The serum level time is relative to the preceeding dose. For example:

• Vancomycin Q 12 hours
• Infused over one hour
• Trough level drawn 30 minutes before the dose

One way to grasp this concept is to understand that the serum level is the result of a dose which has been given, not from a future dose. not from a future dose.

The difference is most likely due to the weight that you are using in your hand calculation. Because creatinine is produced by muscle tissue, C&G recommend that you use lean body weight, except in morbidly obese patients. Because creatinine is produced by muscle tissue, not fat, additional weight in form of fat does not significantly alter the production of creatinine.

There is considerable difference of opinion among practitioners concerning the most appropriate creatinine clearance equation to use. APK© includes multiple creatinine clearance methods from which to choose. Use the method which is most appropriate for your patient. Please refer to this page for more information on creatinine clearance calculations:

Dosing of renally excreted drugs

Enter an infusion length of 90 minutes, which is the average time for IM absorption of aminoglycosides. Be sure to draw your peaks at least 90 plus 15 minutes after the injection.

The program ships without a password.

• The first time you access the edit drug models function it will ask for a password. Before saving the password, the APK© program will ask you to reenter the password to confirm it.
• Thereafter, this will be your password required to access the edit drug models function, so choose one that you can easily remember.
• If you should lose or forget your password, contact the author for help in recovering it.

You do not have to assume steady-state if you use the 3-point method. Draw a trough before the 600mg dose, a peak after, then a mid-point level after that. The program will use the pre-dose trough and the peak level to calculate the volume of distribution. The two post-dose levels are used to calculate the elimination rate.

Please refer to this consensus document which appeared in the June 1997 issue of the International J. of Clinical Pharmacology and Therapeutics:

• Read "Once daily dosing of aminoglycosides"
• The PK/PD principles underlying the Hartford and consensus nomograms are sound. However many consider the nomogram approach to be an oversimplification. Patients should be individually dosed in order to maximize therapeutic efficacy and minimize the risk of toxicity. The dose should be large enough dose to produce a peak that is 8 to 10 times greater than the MIC. The dosing interval should then be extended to produce a trough less than 0.5 mcg/ml in order to provide a washout of aminoglycoside in the renal tubule thereby reducing toxicity.

The initial pediatric calculations are weight based, as they are in every pediatric reference book you will find. Although you cannot target a specific peak and trough, the program will show estimated peak and trough levels from your selected dose.

The reason that initial doses are weight-based is because the creatinine clearance equations for peds are not accurate enough to be used for pk modeling.

Times are relative the beginning and the end of the infusion.

• For pre-dose times, this refers to the beginning of the infusion, hence the instruction "minutes BEFORE infusion".
• For post-dose times, this refers to the end of the infusion, hence the instruction "hours AFTER infusion".

Unfortunately, late doses can not be avoided, so how can you use these levels? There are at least two late dose scenarios, each would be handled differently, depending on the methodology you are using.

The first late dose scenario we'll describe occurs if the dose was late but the levels were correctly drawn relative to the actual hang time. For example, the nurse is supposed to be giving gent 80mg Q 8 hours, at 6-14-22, but the sample dose is given late, at 1600. The trough was drawn at 1530 and the peak at 1730. As you can see, the levels are correctly drawn relative to the late dose.

First, let's examine the Sawchuk and Zaske method. This method is the gold standard for evaluation of peak and trough levels in the one-compartment open model. Sawchuk and Zaske drew three levels: a trough before the dose, a peak after the dose, and another trough after the dose. However, many institutions take a shortcut and only draw two levels, a trough before the dose and a peak after. If the patient is at steady-state, then you can assume that the second trough after the dose will be the same as the trough before the dose. Under most circumstances, this is a valid assumption and will save laboratory expenses.

Next, look at Sawchuk and Zaske's equations for calculating pk parameters, you can find them in the program help file (Press the F1 key). Where is the dosing interval in these equations? ...... nowhere! The dosing interval is not used in any calculation.

If you are using the 3-point method, the interval is not used, and it doesn't matter if the dose was given late, as long as the levels are correctly drawn, relative to the time the dose was actually given.

If you are using the two point method, the dosing interval is only used to extrapolate the pre-dose trough to simulate the after-dose trough. Therefore, in the APK© program, instead of entering the "ordered" interval, you would enter the time between the last dose and the sample dose. Using our same example, if the nurse is supposed to be giving gent 80mg Q 8 hours, at 6-14-20, but the sample dose is given late, at 1600. In the APK© program you would enter an interval of 10 hours. Again, this is because the interval is only used to extrapolate the pre-dose trough.

The second late dose scenario occurs when the dose is give late and the levels are correctly drawn relative to the scheduled hang time, not the actual hang time. For example, if the nurse is supposed to be giving gent 80mg Q 8 hours, at 6-14-20, the sample dose is given late, at 1600, but the trough was drawn at 1330 and the peak at 1530. As you can see the levels are correctly drawn relative to the scheduled dose, not the actual hang time, the "peak" is not a peak at all, but a trough drawn before the dose was given.

This scenario is the result of a lack of communication between lab and nursing. In this case, throw out the peak and just use the trough. With Bayesian you only need a single trough level.

The APK© program is deceptively simple in this area. When you hit a snag like this, you have to stop and think, and that's the downside to having such a simple interface for entering levels. The other alternative, and the one taken by some other PK programs, is to have you enter each and every dose and the time each dose was administered. This approach punishes you each time you have to enter a simple set of levels. The APK© program only makes you work hard in a problem situation.

Please read this step-by-step tutorial, using an Ampicillin 1-compartment model as an example:

• View the APK© model entry tutorial

Unfortunately, this information is not found in one single reference. Bennett's Drug Prescribing in Renal Failure and Chernow's Critical Care Pharmacotherapy have tables of pk data for common drugs. The FDA package insert of newer drugs usually has an excellent pharmacokinetics section.

For a detailed tutorial on creating one compartment models, please see this page:

• View one-compartment tutorial

I have compiled the pk parameters of some common antibiotics into a table on this page:

• View antibiotic pk parameters

Bayesian places significant weight on the population model. Because of this reliance on the population model, it is very important with Bayesian that you pick the right model for your patient. This is a particular problem with vancomycin because of the *extreme* inter-patient variability in pk parameters.

When the program flags an "outlier", it means that, for whatever reason, the serum levels can't be statistically reconciled with the population model. If, after 100 iterations, the Bayesian object (sum of least squares) is not reduced, it gets kicked out of the loop and the patient is labeled an outlier.

Outliers are especially challenging when we are analyzing a single trough level. If the patient's trough is out of range, then you need to get a truer picture of the patient's pk parameters by measuring a peak and trough series instead of a single trough.

If a significant percentage of your patients are flagged as outliers, then there is a good possibility that the model you are using is not appropriate for your patient population. This is a situation where the population analysis tool would be helpful. Each time you print a consult based on serum level data, the calculated pk parameters are saved. This data is a virtual gold mine of information about your patient population. With this tool you can derive a model better fitted to your patients.

The program does not make any specific adjustments for amputees, so you'll need to do some calculations the old-fashioned way. Enter the patient's pre-amputation height. The program will calculate a baseline lean body weight.

Because creatinine is produced by lean tissue, to get a more accurate estimate of CrCl, you'll need to estimate post-amputation muscle mass. Start with the LBW calculated from the patient's pre-amputation height. Then deduct a percentage depending on the extent of the amputation:

• Hand - Decrease LBW by 0.7%
• Forearm and hand - Decrease LBW by 2.3%
• Total arm - Decrease LBW by 4.9%
• Foot - Decrease LBW by 1.5%
• Calf and foot - Decrease LBW by 5.8%
• Total leg - Decrease LBW by 16%

In this case, since your patient is a double amputee, you would decrease the LBW by 32%. Let's call this the Amputee-Adjusted LBW (AALBW).

If the patient's actual weight is less than the AALBW, then the patient is underweight and you should use the patient's current weight to calculate CrCl.

If the patient weighs more than the AALBW, then you should hand calculate the CrCl using the AALBW.

References

1. John Murphy's Clinical Pharmacokinetics, 2nd ed. 2001
2. Brunnstrom, S. Clinical kinesiology. 4th ed. 1983

That is a good question. A patient may also have scoliosis or severe contractions that prevent a true height measurement. There are (at least) three methods that may be used to estimate height when actual measurement is not possible: knee height, forearm length and demi-span.

Estimating height in bedridden patients

APK© may be interfaced with a PIS, using our open interface specification. Please contact your PIS vendor to request implementation.

RxKinetics software interface specs

"Y-intercept less than zero" is displayed when the regression line intercepts the Y axis below zero. "Regression analysis yielded a negative slope" is displayed when the regression line is inverted.

The regression line is a plot of Y vs X where X is creatinine clearance (the independent variable) and Y is the elimination rate (the dependent variable). The Y intercept is the Nonrenal Kel, the slope of the regression line is the Renal Kel for the following equation:

Kel = NonRenalK + [CrCl x RenalK]

Both of these "errors" are caused by a widely scattered data set for which a regression line cannot be accurately calculated. This would be expected with a drug like Vancomycin which has a wide variability in pk parameters. Usually it takes a higher N in your data set before the data becomes analyzable. Keep saving your consults and eventually you will acquire a data set that will give usable results.

The "Bayesian Results" dialog displays several parameters which are used to evaluate the accuracy, reliability, and expected performance of the Bayesian derived model.

Interpreting Bayesian results

APK© has had a built-in update checker since version 3.3.11, it is accessed via the Help menu:

There are four steps to the web update process.

1. Click Check button to access the RxKinetics web site to check for available updates.

   

2. If an update is available, a confirmation dialog will appear. Click the "Yes" button.

   

3. Next, a change log dialog is displayed.

   

4. A running program cannot be replaced.
   Therefore, you must exit APK before installing an update. Web update will not proceed with the install step until you close APK.
   After you have closed the APK program, click the "OK" button to begin the update process.

   

APK© version history

Follow these steps:

1. Copy all data files from your current install folder (usually \Program Files\apk) to a temporary network folder, a floppy disk or any other removable media:
   • apk.ini
   • consults.dbf
   • consults.mdx
   • inactive.dbf
   • inactive.mdx
   • md.dbf
   • md.mdx
   • models.dbf
   • models.mdx
   • patient.dbf
   • patient.mdx
   • users.dbf
   • users.mdx
2. Install APK© onto your new computer from the original installation CD.
   How to obtain replacement installation CD
3. Copy the data files saved in step 1 to the install folder in your new computer.
4. Download and install the latest update patch from the website.

This issue has been resolved in the latest version of APK©. You no longer need WinHlp32.exe. If you are experiencing this problem, please update your APK© installation.

When attempting to access the product help, you may see a message similar to this one:

Beginning with Windows Vista, the Windows Help program (WinHlp32.exe) is no longer included with Windows. Microsoft prohibits redistribution of the Windows Help program.

Yes.

All versions of 64-bit Windows (XP, Vista, 7, 8, 10) are able to run 32-bit programs seamlessly through WOW64 which is provided with the operating system and does not have to be explicitly enabled. In other words, it's 100% automatic. (Ref: Microsoft)

According to Microsoft, 32-bit software running under WOW64 has a similar performance when executing under 32-bit Windows. (Ref: Microsoft)

Check the active task list in your Windows Task Manager (Ctrl+Alt+Del). If it's there, then the APK window is off screen. This behavior is sometimes triggered when you switch between different monitor resolutions and orientations.

How to resolve:

1. Click on the APK icon to start the app.
2. Login blindly, i.e., type your user name, hit tab, type your password, then press enter.
3. Hold the Alt key down and press the space bar. This brings up the Windows move function.
4. Press the M key.
5. Use the Arrow keys to move the window into view. Most likely it is off to the left, so try the right arrow first.
6. When the window comes into view press the Enter key.

The default monitoring form is a Word template. During printing of the form, APK first calls Word to automatically search and replace designated fields, e.g., Patient name, MRN, Allergies, etc. After the blank form is filled in, APK calls the Word print function and returns the document to its original form.

If network connectivity is lost during printing, Word will sometimes save the patient-specific form, replacing the template (thanks Microsoft!).

How to resolve:

1. Exit APK.
2. Navigate to the folder container the APK.exe application.
3. Delete the file named "Blank_PKmonitor.doc"
4. Restart APK.
5. A new form will be automatically recreated.

Specifics of the monitoring form template and field identifiers can be found in the APK help.

An Error #32 which reads "Error erasing" indicates a file is locked by Windows and cannot be modified.

Please read the error message as it tells you which file is locked. In this example it is "consults.MDX":

1. Exit APK© if open.
2. Open Windows File explorer and navigate to the APK© folder.
3. Delete the index file listed in the dialog.
   In the example above it is "consults.MDX"
   • Do NOT delete consults.DBF.
4. Restart APK©, the index will automatically be rebuilt.

Error #33 (file lock violation) indicates one or more of the lock files are corrupt or inaccessible. Lock files have the "@S@" extension and are used to keep track of which records are open and which are locked for writing. Lock files are the gate-keepers of the database, allowing multiple users to simultaneously access records without corrupting the underlying data.

1. The most frequent cause of Error #33 is inadequate user access rights and privileges.
   • All users must have full read and write access to the folder where APK© resides.
2. A hard network or PC crash is also another common cause of this error.
   • Navigate to the APK© folder and delete all files with the extension "@S@".
3. If you are running a Novell Network, lock file violation is a known bug with version 4.83 of the Client for Windows NT/2000/XP.
   • Please install the latest Client patch from Novell.
4. And finally, Error #33 has been traced to certain network maintenance tasks.
   • Ensure that all users exit the APK© program before they go home.

The occurance of file lock violations has been greatly reduced in newer versions of APK©. If you are running an older version, please update your APK© installation. Updates are freely available for download from this website, it is your responsibilty to keep the software updated.

Error #221 (Index file not open) usually indicates a malformed index file for the CONSULTS database.

1. Open Windows File explorer and navigate to the APK© folder.
2. Delete the index file "consults.MDX".
   • Do NOT delete consults.DBF.
3. Restart APK©, the index will automatically be rebuilt.

Error #222 (Index file corrupted) is usually caused by sudden loss of power or a network server failure. To repair the index: delete the corrupted index files, then restart APK©.

1. Start Windows explorer and open the APK© folder.
2. Delete these two files:
   • "patient.mdx"
   • "inactive.mdx"
3. Restart APK©, the index will automatically be rebuilt.

Error #227 (Insufficient disk space) is seen with old versions of APK© running on very large disk partitions (one terrabyte or greater).

• Please update your APK© installation.
• Updates are available for download from this website.
• Updates are free, it is your responsibilty to keep the software updated.

Lock file errors like #1202 and #33 usually occur when someone has APK© open on a laptop and loses WIFI network connectivity. An unexpected power outage is another cause.

To fix the problem delete the file listed on the dialog. In the screen grab above the file is PATIENT.@S@:

1. Open Windows File explorer
   • Turn on "View file extensions"
2. Navigate to the APK folder
3. Delete the file named PATIENT.@S@
   • Make double damn sure you have selected this specific file for deletion!