We recently completed a week-long set of meetings with the FDA, where we met with over 300 FDA reviewers from 7 of the 11 FDA centers that use Phoenix. Here are a few topics that took center-stage during our visits: Q: How can we create Phoenix workflow templates that are reusable across different studies with … Continued
In teaching pharmacometrics, I’ve noticed that scientists have difficulty with certain PK/PD modeling concepts. Maybe you’ve read about some of these terms in journal articles, but didn’t know what they meant? Or you’ve heard these terms bandied about by colleagues, but felt too shy to ask them what they meant? I’ll clarify some important concepts … Continued
Over the course of my career, I have taught the theory and practical applications of PK/PD modeling to hundreds of scientists. In this blog post, I’ll share some of my most popular tips for solving common difficulties encountered by pharmacometricians. The tools of the trade While I have worked with a number of pharmacometrics tools, I … Continued
Calculating area under the curve requires the use of two separate equations: one is follows the “linear trapezoidal rule” and the other follows the “logarithmic trapezoidal rule.” These equations are normally presented in textbooks without derivations so all you have to do is insert the concentrations and times and you can calculate the area under … Continued
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 … Continued
PK/PD modeling is an exciting are of research in clinical pharmacology. Most often we try to model the effect of a drug by drawing relationships between the concentration and effect. This usually entails subsetting the data to exclude information from subject that received placebo during the trial. But statistical comparisons in clinical studies are most … Continued
At the request of a reader, I have decided to extend my series on bioanalysis to include another topic: calibration curves. The calibration curve is they keystone of bioanalysis. It is what links the instrument response to a specific concentration of drug. It is like the magic decoder ring that helps you decipher the hidden … Continued
In this final post regarding bioanalysis, I will review a few of the main ideas related to bioanalytical method validation. The purpose of a method validation is to demonstrate that a specific bioanalytical method can reliably determine the concentration of drug in a study sample with a high degree of confidence. Validation does not mean … Continued
One of the oldest methods used for the quantitation of drug molecules is radiometric analysis. This generally involves quantitation of radiation from beta-emitting radioactive isotopes such as 14C, 3H or 32P. Radiometric analysis is one of the most precise, sensitive, and efficient detection methods; however, there are many technical and social challenges with using this … Continued
Our discussions of various bioanalytical methodologies over the past few weeks has focused on chromatography and small molecule analysis. Today we are going to discuss a collection of methods that is commonly used for large molecules, such as peptides, peptides and macro-molecules. These molecules are often called “biologics” because they are generally derived from endogenous … Continued
