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 … Continued
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 … Continued
Prediction of metabolic clearance in extreme individuals rather than the ‘average human’ is becoming an attractive tool within the pharmaceutical industry. The current study involved prediction of variability in metabolic clearance for alprazolam, triazolam and midazolam with emphasis on the following factors: first, evaluation of clearance prediction accuracy using intrinsic clearance (CLint) data from in … Continued
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 … Continued
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 … Continued
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 … Continued
