# Physiologically Based Pharmacokinetic Model of Magnesium Implant Absorption and Distribution in Tissue and Organs

## TL;DR

This paper presents a model to predict how magnesium from implants accumulates in the body over time, highlighting risks for vulnerable patients.

## Contribution

The study introduces the first PBPK model for magnesium implant accumulation, enabling patient-specific predictions.

## Key findings

- Tissue and bone compartments significantly influence long-term magnesium serum levels due to their large volume.
- Magnesium accumulation can take months to years, necessitating monitoring for at-risk patients.
- The model uses simple patient measurements, offering a practical framework for biodegradable implants.

## Abstract

The long-term accumulation
of magnesium (Mg­(II)) ions in human
patients resulting from the biodegradation of clinical Mg (alloy)
implants is investigated using a physiologically based pharmakinetic
(PBPK) mathematical model. In severe cases, an excess of Mg in blood
(hypermagnesemia) causes a range of health concerns and potentially
death. Studies investigating clinical Mg devices generally indicate
that there is little risk in healthy patients; however, there is concern
that excessive Mg accumulation may occur in patients who are elderly,
have osteoporosis, and/or have renal disease. The PBPK model describes
the time evolution of Mg concentrations in blood, tissue, and bone
compartments in response to Mg sourced from diet and implant(s) devices,
over the implant’s lifetime. It predicts that Mg absorption
in the tissue and bone compartments is the key factor in modulating
long-term serum levels due to their large volume and Mg load. Furthermore,
the time scale of observable accumulation can take several months
to years, suggesting that for vulnerable patients, the Mg levels should
be monitored throughout the lifespan of an Mg implant. Most of the
model parameters can be estimated from simple patient measurements;
thus, the model is the first step toward a practical patient-specific
framework for Mg and for other biodegradable implant devices to inform
medical treatments in response to the potential long-term accumulation
of biodegraded products.