PMXSolutions.com

This website was created to increase the documentation in the field of pharmacometrics. The website contains blog posts, pharmacometric tutorials, Shiny applications and a lot of example codes for R, mrgsolve and for NONMEM. All related to data analytics, population PK/PD, PBPK and pharmacometrics in general.

Latest posts

New shiny applications for PMX simulations!

A range of new shiny applications have been published on this website to visualise pharmacokinetic profiles over time and better understand the use of population models. All applications can be accessed from the Applications menu on this website. PK profile over time Simulate an oral pharmacokinetic profile based on the dose and model parameters. Profiles can be saved in a …

Publishing the covariance matrix of population models. Why not?

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 …

Parallel fast-slow absorption – Modelling the Tortoise AND the Hare

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 …

Applying MAP Bayes estimation for therapeutic drug monitoring (TDM) in R with mrgsolve

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 …

Simulating the equi-dosing regimen region in R using mrgsolve – a bottom-up approach

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 …

How (not) to report pharmacokinetic data

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 …

Inter-individual and/or inter-occasion variability: what can we quantify in our models and what is the impact on simulations

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 …

Calculating the power of covariates in population non-linear mixed effects models: the Monte Carlo Mapped Power approach

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 …

Flawed study design of parent-metabolite pharmacokinetic studies – the prove is in the pee

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 …

Celebrating 15.000 visitors by going open source!

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 …