Project Title: Mathematical model of pharmacokinetics for personalized optimization of metformin therapy

Project No: lzp-2018/2-0088

Period: 1. December, 2018 – 30. November, 2020.

Project costs: 200 000 EUR

Principle Investigator: PhD Egils Stalidzāns

Collaboration partner: University of Latvia

Summary

The popular drug metformin is used for the treatment of more than 120 million patients with Type 2 Diabetes mellitus and other diseases. Transport of metformin through tissues and body fluids is characterized with high variation among individuals due to genetic variants found in metformin transporters coding genes  (OCT1, OCT2, OCT3, PMAT, MATE1 and MATE2). As a result,  metformin concentration in target tissues do not correspond to required therapeutical levels leading to overprescription of the drug. It is necessary to investigate relation between particular genetic variants and the peculiarities of metformin transport in the human body in order to improve current drug prescription algorithm.

The project idea is to apply more than ten years of medical and pharmacological expertise of pharmacogeneticists with more than ten years of experience of computer scientists and information technologists with ordinary differential equation systems based dynamic modeling of bioprocesses. Already obtained experimental data from metformin pharmacokinetics study  in combination with genetic information will serve for parametrisation of personalized dynamic mechanistic model. The model will enable to develop suggestions for minimisation of dose and optimisation of metformin administration to reach best effect possible for each genetic profile investigated.

This approach of systemic mathematical modeling can be extended to studies of pharmacokinetics of other pharmaceutical compounds as well.