The Certara Blog

Author: Nathan Teuscher

Dr. Nathan Teuscher is the Vice President of Pharmacometric Solutions at Certara. He is an expert in clinical pharmacology, pharmacometrics, pharmacokinetics and pharmacodynamics and was trained by David Smith at the University of Michigan. Dr. Teuscher has held leadership positions in biotechnology, pharmaceutical and contract research companies. In 2008 he established the Learn PKPD.com website to share his knowledge with the community. Prior to coming to Certara, he was the Founder and President of PK/PD Associates.

Recent Posts

Accumulation - What It Means and How to Calculate It

Accumulation: What It Means and How to Calculate It

A reader, Michael, asked me to discuss the concept of accumulation. This term is used frequently in both the nonclinical and clinical setting. Some people use the word with fear, while others explain it in complicated terms. Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug. When the […]

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Bioavailability

Bioavailability

The term bioavailability is used very frequently in pharmacokinetic discussions. Often it is misused and complicated by those who don’t understand its meaning. Bioavailability simply means the fraction of administered drug that reached the systemic circulation (blood). It can range from 0% (no drug) to 100% (all of the administered drug). Absolute vs Relative The […]

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Designing a Clinical Drug-drug Interaction Study

Designing a Clinical Drug-drug Interaction Study

After a much longer delay that I expected, I am back to blogging on a regular basis. Today I want to discuss a common topic among clinical pharmacologists. How do you properly design a drug-drug interaction study? Defining drug-drug interactions While these studies may appear complicated, they can be simplified very quickly to make the […]

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What is Hysteresis in PK/PD Analysis?

What is Hysteresis in PK/PD Analysis?

I apologize to all my readers for such a long lapse between posts. After a very busy summer and fall, I am back to posting regularly to my blog about PK/PD topics. When analyzing PK/PD data, one of the most important plots used to visualize the data is to plot time-matched PK/PD data on a […]

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

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

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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What is Curve Stripping?

What is Curve Stripping?

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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Phoenix Software Review

Phoenix NLME Software Review—Part 3

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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Phoenix Software Review

Phoenix WinNonlin Software Review—Part 2

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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Phoenix Software Review

Phoenix WinNonlin Software Review—Part 1

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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Are There Too Many PhDs?

Are There Too Many PhDs?

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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How to Set Your Target Limit of Quantification

How to Set Your Target Limit of Quantification

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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What to Do with Those BLQs!

What to Do with Those BLQs!

BLQ values are like those pimples we used to get as teenagers. They often show up at the worst time and they always seem to be in the wrong place. (Is their really a “right” place for a pimple!?) Then what do you do with the pimple? Rub some alcohol on it, put other medication, […]

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Calculating AUC (Linear and Log-linear)

Calculating AUC (Linear and Log-linear)

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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The Difference Between Vd and Vss

The Difference Between Vd and Vss

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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What is Shrinkage?

What is Shrinkage?

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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Is a Monte Carlo Simulation an Exotic Drink?

Is a Monte Carlo Simulation an Exotic Drink?

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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What is WinNonlin?

What is WinNonlin?

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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What is the Difference Between Individual and Population PK?

What is the Difference Between Individual and Population PK?

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

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

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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Why Should You Evaluate Dose Proportionality?

Why Should You Evaluate Dose Proportionality?

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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