PK/PD Modeling & Simulation

How Can PK/PD Analysis Add Value to Patient Care?

Nathan Teuscher

In May 2011, T.J. Smith and B.E. Hillner published an opinion piece in the New England Journal of Medicine titled “Bending the Cost Curve in Cancer Care” (link). In this opinion piece, Smith and Hillner suggest that the rapidly increasing cost of treating cancer is not sustainable. “We must find ways to reduce the costs […]

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Topics: PK/PD Modeling & Simulation

What is Curve Stripping?

Nathan Teuscher

The process of curve stripping is used in both compartmental and non-compartmental analysis. Each pharmacokinetic profile is made up of one or more exponential phases. The “curve stripping” process extracts each of these exponential phases from the pharmacokinetic profile in a manual fashion that does not require non-linear curve fitting. This method was originally used […]

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Topics: PK/PD Modeling & Simulation

Phoenix NLME Software Review—Part 3

Nathan Teuscher

In this third and final post about by review of the Phoenix WinNonlin software, I review the newest feature of the software and provide overall thoughts. You can read about the Phoenix platform in Part 1 of my review, and the non-compartmental and single subject analysis in Part 2 of my review. With the exception […]

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Topics: PK/PD Modeling & Simulation

Phoenix WinNonlin Software Review—Part 2

Nathan Teuscher

Part 2 of the WinNonlin review will cover the non-compartmental and PK modeling functions of Phoenix WinNonlin. To many people, these two features have defined WinNonlin for many years. And the updated software does not disappoint with significant improvements to the functionality, ease of use, automated graphics, and other features. As I discussed in Part […]

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Topics: PK/PD Modeling & Simulation

Phoenix WinNonlin Software Review—Part 1

Nathan Teuscher

WinNonlin by Certara has been a fixture in pharmacokinetic analysis software for over 20 years. While it has been known as a tool for non-compartmental analysis and model-based analysis of single subject data, the new Phoenix WinNonlin creates an entirely new platform for pharmacokinetic and pharmacodynamic analysis. Similar to my other reviews. I will be evaluating features […]

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Topics: PK/PD Modeling & Simulation

Are There Too Many PhDs?

Nathan Teuscher

Elizabeth Weise, a USA Today journalist, posted a story titled “Journals: USA, others need to re-tool their science programs” on April 22, 2011 (link). The premise of the article is that the journal Nature is reporting that there are not enough academic positions available for the number of PhD graduates, and that non-academic industries are […]

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Topics: PK/PD Modeling & Simulation

How to Set Your Target Limit of Quantification

Nathan Teuscher

One of the key things to do during the transition from preclinical development studies to clinical development studies is to set the target for your drug assay limit of quantification (LOQ). I will outline a few considerations on that topic. Here are my main assumptions: You are working with a drug that is intended for […]

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Topics: PK/PD Modeling & Simulation

Calculating AUC (Linear and Log-linear)

Nathan Teuscher

When performing non-compartmental analysis, the area under the concentration-time curve (AUC) is calculated to determine the total drug exposure over a period of time. Together with Cmax, these two parameters are often used to define the systemic exposure of a drug for comparison purposes. For example, in bioequivalence trials, the entire statistical analysis is based […]

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Topics: PK/PD Modeling & Simulation

The Difference Between Vd and Vss

Nathan Teuscher

There are many terms used to represent volume of distribution, but two common ones are Vd and Vss. Vd is the apparent volume of distribution. It can be calculated using the following equation: Vss is the apparent volume of distribution at steady state. Or, the sum of all volume terms in a multicompartment model. It […]

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Topics: PK/PD Modeling & Simulation

What is Shrinkage?

Nathan Teuscher

In 2007, Mats Karlsson and Radojka Savic published a perspective in Clinical Pharmacology & Therapeutics titled “Diagnosing Model Diagnostics.” In this article they examined the use of diagnostic plots to evaluate the adequacy of model fits for nonlinear mixed-effects analysis. Although there is a wealth of information in this article, the population PK analysis community […]

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Topics: PK/PD Modeling & Simulation

Is a Monte Carlo Simulation an Exotic Drink?

Nathan Teuscher

The term “Monte Carlo simulation” is often used in the modeling and simulation literature with PK/PD analysis. When I was first exposed to this term, I was thoroughly confused and thought that it was some exotic statistical method that required 3 PhDs and a few days to comprehend. Well, I was very wrong. A Monte […]

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Topics: PK/PD Modeling & Simulation

What is WinNonlin?

Nathan Teuscher

A reader suggested that I write a similar post about WinNonlin. Great idea! Thank you! WinNonlin is a pharmacokinetic software package that has grown and evolved over the past 20 years. The most familiar versions of WinNonlin (v3 – v5) were stand-alone Windows-based software packages used to perform non-compartmental analysis and single subject non-linear model […]

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Topics: PK/PD Modeling & Simulation

What is the Difference Between Individual and Population PK?

Nathan Teuscher

Pharmacokinetic analysis is often broken into two areas … “PK” and “population PK”. Sometimes the first term “PK” is also called “individual PK”. I’d like to demystify these two analysis methods in this post. In the analysis of biological samples, we have many different detection technologies, for example mass spectroscopy, UV spectroscopy, radiometric detection, and […]

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Topics: PK/PD Modeling & Simulation

Blood or Plasma? Which Should You Assay for Drug Concentration?

Nathan Teuscher

Since modern drug development, drug concentration assays have almost exclusively used plasma as a matrix rather than whole blood. Various theories about assay sensitivity, matrix interference, protein binding, and free drug movement have been put forth to explain why it is “best” to measure drug concentrations in plasma. Personally none of these theories convinces me […]

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Topics: PK/PD Modeling & Simulation

Why Should You Evaluate Dose Proportionality?

Nathan Teuscher

Dose proportionality is a common phrase used pharmacokinetics. Early in the pre-clinical development process, we evaluate dose proportionality in animal species. Then if the drug advances to clinical trials, one of the first assessments in humans is to evaluate dose proportionality. Why is it so important? What do we learn from understanding dose proportionality? What […]

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Topics: PK/PD Modeling & Simulation

What is the Difference Between PK and TK?

Nathan Teuscher

PK is the abbreviation for pharmacokinetics. TK is the abbreviation for toxicokinetics. Some consider these to be distinct specialties while others consider them to be the same. Let me explain and then I would like to see what you think. Pharmacokinetics generally deals with doses that are in a therapeutic range. Thus common dose ranges […]

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Topics: PK/PD Modeling & Simulation

Why are PK Parameters Lognormally Distributed?

Nathan Teuscher

The statistical analysis of pharmacokinetic parameters is often overlooked and not always well understood. The disconnect between the pharmacokineticist and the biostatistician can often be a huge stumbling block that prevents the appropriate analysis of PK parameters. While I cannot solve all the disagreements between pharmacokineticists and biostatisticians in a single blog post, I hope […]

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Topics: PK/PD Modeling & Simulation

What are Direct and Indirect Pharmacodynamic Models?

Nathan Teuscher

When constructing pharmacodynamic (PD) models, you will often encounter the adjectives “direct” and “indirect” describing the associated PD model. This terminology was very confusing to me when I was learning about PD modeling. Hopefully a brief explanation will help you. Let’s start with the direct PD model. In this type of model, the drug is […]

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Topics: PK/PD Modeling & Simulation
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