How Does the In Vivo Biliary Elimination of Drugs Change with Age? Evidence from In Vitro and Clinical Data Using a Systems Pharmacology Approach

Information on the developmental changes in biliary excretion (BE) of drugs is sparse. The aims of this study were to collate literature data on the pharmacokinetics of biliary excretion of drugs used in pediatrics and to apply a physiologically-based pharmacokinetic (PBPK) model to predict their systemic clearance (CL) with a view to elucidating age-related changes […]

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Potential Sources of Inter-subject Variability in Monoclonal Antibody Pharmacokinetics

Understanding inter-subject variability in drug pharmacokinetics and pharmacodynamics is important to ensure that all patients attain suitable drug exposure to achieve efficacy and avoid toxicity. Inter-subject variability in the pharmacokinetics of therapeutic monoclonal antibodies (mAbs) is generally moderate to high; however, the factors responsible for the high inter-subject variability have not been comprehensively reviewed. In […]

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Calculating the Elimination Rate Constant

Nathan Teuscher

The elimination rate constant is the rate at which drug is cleared from the body assuming first-order elimination. Various abbreviations are used to represent the elimination rate constant including ke, kel, λ, and λz. The calculation of the elimination rate constant can be done using pharmacokinetic parameters or it can be done directly from a […]

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Topics: PK/PD Modeling & Simulation

Bioanalysis from a PK Perspective

Nathan Teuscher

The field of bioanalytical chemistry, or bioanalysis, is an important area of research that has a direct impact on the work of pharmacokineticists. Essentially, bioanalysis converts a blood sample (or any other matrix) into a drug concentration by the use of analytical equipment. Over the next few weeks, I would like to cover a variety […]

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Topics: PK/PD Modeling & Simulation

What Can We Learn from Dose Normalization?

Nathan Teuscher

Dose normalization is a common calculation performed with pharmacokinetic parameters. The general process is to divide the PK parameters by the administered dose. This is performed for each individual or treatment group in a study, and then comparisons of dose-normalized parameters can be performed. But, why would we want to dose normalize PK parameters? What […]

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Topics: PK/PD Modeling & Simulation

Extrapolating AUC to Infinity

Nathan Teuscher

Area under the curve or AUC is a pharmacokinetic statistic used to describe the total exposure to a drug. More specifically, it is the time-averaged concentration of drug circulating in the body fluid analyzed (normally plasma, blood or serum). Standard calculation of AUC involves using non-compartmental techniques to calculate the AUC from time 0 to […]

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Topics: PK/PD Modeling & Simulation

Simplifying Deconvolution

Nathan Teuscher

Deconvolution is used to evaluate the absorption kinetics of a drug. Unfortunately the term can be confusing and explanations are generally even more confusing. While deconvolution is not a simple topic, I believe it can be understood so that more scientists can apply the principles to their work. Before I define deconvolution, let me define […]

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Topics: PK/PD Modeling & Simulation

What is “Adjusted” r-squared?

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Review of Phoenix Connect Software Tool

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

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

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

The Superposition Principle

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Saturable Drug Absorption

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Nonlinear PK: What Does That Mean?

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

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

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Changing Column Names and Units in Phoenix WinNonlin

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

How to Filter Data with Phoenix WinNonlin

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Calculating Urine PK Parameters

Nathan Teuscher

Pharmacokinetic analysis normally focuses on systemic exposure to a drug; however, much can be learned from urinary pharmacokinetic parameters. Urinary PK parameters tell you about how much drug was absorbed (at a minimum), and how much drug is eliminated through the kidney. Often it provides easy access to metabolites that are also eliminated in the […]

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Topics: PK/PD Modeling & Simulation

Accumulation: What It Means and How to Calculate It

Nathan Teuscher

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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Topics: PK/PD Modeling & Simulation

Bioavailability

Nathan Teuscher

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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Topics: PK/PD Modeling & Simulation
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