## 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.

## Understanding Steady State Pharmacokinetics

“Steady state” is an important term in pharmacokinetics, but it can often seem a bit abstract and confusing to many. Here is how I define steady state: When the rate of drug input is equal to the rate of drug elimination, steady state has been achieved. Another way to think of this is imagine a […]

## What is Identifiability?

Developing models for pharmacokinetic or pharmacodynamic data requires creativity, patience, and hard work. Sometimes that creativity ends up violating mathematical principles which can lead to poorly fitting models and frustration for a modeler. One common area where mistakes are made is related to the analysis of parent and metabolite data simultaneously. Because data are available […]

## What is the -2LL or the Log-likelihood Ratio?

If you have ever read the literature on pharmacokinetic modeling and simulation, you are likely to have run across the phrase  “-2LL” or “log-likelihood ratio”. These are statistical terms that are used when comparing two possible models. In this post, I hope to explain with the log-likelihood ratio is, how to use it, and what […]

## Using Sampling “Windows” for PK Blood Samples

One of the most common questions posed by clinical operations experts when including pharmacokinetic sampling in a clinical trial is the following: “What is the time window we should allow for each blood sample?” My answer is always the same: “Don’t include any window.” I am almost always met with a confused look. The confusion is […]

## What is “Adjusted” r-squared?

Linear regression is a common tool that the pharmacokineticist uses to calculate elimination rate constants. Standard linear regression provides estimates for the slope, intercept, and r2, a statistic that helps define goodness of fit. Statistical texts define r2 as the coefficient of determination and it is calculated using the following equation: where SS = the sum of […]

## Demystifying CDISC, SDTM, and ADaM

Team discussions regarding CDISC often bring in the mists of darkness, which obscure the landscape and prevent us from moving in a clear direction. Then if we weren’t confused enough, the discussion moves to SDTM, ADaM, and clinical databases, and we feel like we are spinning out of control. The land of clinical study data can […]

## Understanding Accelerator Mass Spectrometry

Accelerator mass spectrometry (AMS) is an analytical method used to detect the amount of radioactive carbon in a biological sample. It is an extremely sensitive methodology that can be used in early clinical research when conventional radiometric detection methods such as liquid scintillation counting are not possible. AMS is a powerful technique; however, it is […]

## Why Do We Customize Aminoglycoside Dosing?

Aminoglycosides are a class of molecules that are used for the treatment of serious gram-negative systemic infections. Some common aminoglycosides are tobramycin, gentamicin, amikacin, and neomycin. Aminoglycosides have bactericidal activity against most gram-negative bacteria including Acinetobacter, Citrobacter, Enterobacter, E. Coli, Klebsiella, Proteus, Providencia, Pseudomanas, Salmonella, Serratia and Shigella. Aminoglycosides are also active against most strains of Staphylococcus aureus and S. epidermidis. Most strains […]

## Review of Phoenix Connect Software Tool

In this post, I am reviewing the Phoenix Connect package from Certara. Over the past several years, Certara has made a significant effort to modernize the pharmacokinetic analysis software tools to aid in the drug development process. While many longtime users of the PCNonlin and WinNonlin software solutions are disappointed with the need to learn […]

## Mean Residence Time (MRT): Understanding How Long Drug Molecules Stay in the Body

When I first began learning about pharmacokinetics, I was often confused by the mean residence time (MRT) parameter. I wasn’t really sure what it meant, how to interpret the value, and why it would ever be important. After many years of working with pharmacokinetic analysis, I still do not use MRT very often, but I […]

Drug therapy in chronic disease situations requires systemic drug levels to reach target steady-state levels for maximum safety and efficacy. The time it takes for a drug to reach steady-state is a function of the elimination half-life of the drug. The following table illustrates how long it will take to achieve steady-state relative to the […]

## The Superposition Principle

The superposition principle has nothing to do with a super-hero; however, you might be perceived as a hero if you can explain the principle to others. The superposition principle is a mathematical concept that helps us analyze concentration-time data. While it may seem complicated, it is actually nothing more than addition! The superposition principle states […]

## Saturable Drug Absorption

Drug absorption is the process by which a drug molecule moves from the site of administration to the systemic circulation. Following intravenous administration, there is no absorption process since the drug is directly introduced into the blood stream. However, for oral, intramuscular, subcutaneous, sublingual, buccal, transdermal, (and many other routes), there will be an absorption […]

## Nonlinear PK: What Does That Mean?

You may come across a phrase like the following and wonder what it means: “… this drug exhibits nonlinear pharmacokinetics …”. An example of a drug that has nonlinear pharmacokinetics (PK) is erythropoietin or EPO. You may have heard about EPO in the context of sports because it is a performance enhancing drug (PED). EPO […]

## Why Cmax is a Continuous Variable and Tmax is a Categorical Variable

The maximum observed concentration (Cmax) and the time of Cmax (tmax) are both obtained directly from the concentration-time data. In this post, I will review how to determine both of these parameters, and how to interpret information from the values. These two parameters are simple, but they pack some important information if you know how […]

## What is Quantification Anyway?

Bioanalytical analysis is a fundamental tool for the pharmacokineticist. The results of a bioanalysis are the source data for all pharmacokinetic work. Thus a clear understanding of the methodologies and challenges associated with the bioanalytical analysis science is of great benefit to a pharmacokineticist. As an example, I was recently working on the development of […]

## Changing Column Names and Units in Phoenix WinNonlin

One of the most common tasks when working with data in Phoenix WinNonlin is to change the column titles or units. In many software packages that consists of clicking on the data spreadsheet and re-typing the new information; however, with Phoenix, you have to take a few additional steps. Here’s some quick tips on how […]

## How to Filter Data with Phoenix WinNonlin

Phoenix WinNonlin is Certara’s new implementation of the popular pharmacokinetic software that has been the mainstay of non-compartmental analysis for over 15 years. But, this newest version is the biggest change in the software since the original PC Nonlin was converted to the Windows-based “WinNonlin” (i.e. Windows Nonlin). In Phoenix WinNonlin, there are a powerful […]