Supplementary information files for "Physiologically based pharmacokinetic model of magnesium implant absorption and distribution in tissue and organs"

Supplementary files for article "Physiologically based pharmacokinetic model of magnesium implant absorption and distribution in tissue and organs"<br><br>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, 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 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 timescale 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 a first step towards 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.