With the introduction of ChatGPT I was interested to learn how ChatGPT in pharmacometrics might be applied and how this will impact my code writing tasks, especially for doing pharmacokinetic analysis and creating a starting point for basic R applications. My objective of this post was to see whether ChatGPT could write the R code for a shiny application that …
This page provides an overview of the abbreviations and terminology commonly used in population PK/PD articles.
The information in the covariance matrix Everyone that has worked for longer than a day with NONMEM has a high probability of encountering error messages mentioning the covariance matrix (nonpositive semidefinite…, R matrix algorithmically singular…, etc.) or people ask and discuss whether or why the covariance step of the model was not successful. However, we barely pay any attention to …
Introduction Unsurprisingly, the absorption of drugs is a complex process. Should you try a first-order input? Zero-order? Both?! Especially when a bias in the model fit of your absorption phase is visible, you should pay some attention on quantifying parallel absorption processes. Multiple absorption processes in one model may be used to describe complex absorption profiles of drugs. Indeed, a …
The development of population PK (and PD) models enable the use of individual Bayesian dose optimization. One could use the included covariates to derive the dose of an individual but one could also determine what an individual’s clearance and/or volume of distribution is by measuring one or multiple plasma concentrations after the first dose. Especially when a narrow therapeutic window …
Acknowledgments The idea for this post was based upon the research by Dr. Lloyd Bridge, presented at the British Pharmacological Society meeting December 2018. and published in October 2020 in JPKPD: Hof, F., Bridge, L.J. Exact solutions and equi-dosing regimen regions for multi-dose pharmacokinetics models with transit compartments. J Pharmacokinet Pharmacodyn (2020). https://doi.org/10.1007/s10928-020-09719-8 Introduction When a PK(/PD) model is developed, it is …
The correct reporting of pharmacokinetic data can provide a tremendous amount of information on the clinical pharmacological characteristics of a drug. Small studies with a limited number of plasma samples can already be informative for others, especially in special populations where information is already limited. However, regardless of the sample size of the study, from extensive phase 1 studies to …
Introduction We are not all the same. We know that there is variability originating from physiological differences in the pharmacokinetic and pharmacodynamic (PK/PD) processes between individuals in a population, also called the inter-individual variability or IIV. We also know that the there can be changes in these processes from one day to another, or between two dose administrations, which is …
This post is based on the work of, among others, Camille Vong and the hands-on course about the MCMP given by Rob ter Heine and Elin Svensson. Read and cite the following publications when using an MCMP analysis in your next project: https://link.springer.com/article/10.1208%2Fs12248-012-9327-8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791488/ Power You have probably heard people talk about the power of a study. In short, what …
How do we develop a ‘standard’ population PK model? We obtain blood/plasma concentrations over time of the drug of interest, in multiple individuals, and we apply our population NLME modelling techniques to quantify the parameters. This data is sufficient to provide us with information on the absorption rate constant, the volume of distribution, the clearance, and the inter-individual variability in …
In 2019 alone, PMXSolutions.com has been visited by over 15.000 visitors! In order to celebrate this overwhelming interest in the website, I have made the Shiny application for pharmacokinetic simulations open source on GitHub! Visit the GitHub repository https://github.com/michielve/PMX_Simulations Collaborate on code GitHub is a great platform to share and collaborate on coding projects. Feel free to use and improve …
A modellers challenge: getting data in front of you that don’t seem to fit any of the standard effect models and PKPD relationships. Especially in endocrinology, hormonal profiles are rarely in steady-state and vary constantly over time, complicating the application of NLME models. In this post I will discuss 3 degrees of pulsatile profiles on 3 model hormones: Circadian rhythm …
