PK/PD Modeling & Simulation

Cassette Dosing: Advantages and Challenges

Nathan Teuscher

Cassette dosing is a technique primarily used in drug discovery efforts in non-clinical studies to collect pharmacokinetic data from multiple drug candidates in a single experiment. A typical cassette dosing pharmacokinetic study involves simultaneous administration of 5-10 compounds to a set of animals. Serial blood samples are obtained and LC/MS/MS techniques are used to measure […]

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Topics: PK/PD Modeling & Simulation

What is GLP (Good Laboratory Practice)?

Nathan Teuscher

Good laboratory practice or GLP is a set of principles intended to assure the quality and integrity of non-clinical laboratory studies that are intended to support research or marketing permits for products regulated by government agencies. The term GLP is most commonly associated with the pharmaceutical industry and the required non-clinical animal testing that must […]

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Topics: PK/PD Modeling & Simulation

What is Identifiability?

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

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

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Using Sampling “Windows” for PK Blood Samples

Nathan Teuscher

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 […]

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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

Demystifying CDISC, SDTM, and ADaM

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Understanding Accelerator Mass Spectrometry

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation

Why Do We Customize Aminoglycoside Dosing?

Nathan Teuscher

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 […]

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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

What is a Loading Dose?

Nathan Teuscher

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 […]

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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

What is Quantification Anyway?

Nathan Teuscher

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 […]

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Topics: PK/PD Modeling & Simulation
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