open-systems-pharmacology / creatinine-model

Creatinine-Model

Whole-body PBPK model of creatinine as MATE1 and OCT2 biomarker

Repository files

Within this repository, we distribute a whole-body PBPK model of creatinine, that has been carefully developed using a large number of clinical studies and evaluated within our drug-biomarker interaction modeling network. The model applies endogenous synthesis in muscle cells, active tubular secretion via OCT2 and MATE1 as well as diurnal variation. Additionally, the model can describe increased creatinine concentrations in plasma after ingestion of differently prepared meat meals.

The MoBi project file contains simulations of clinical studies utilized during model establishment, including the respective observed data [1][2][3][4]. For further details, quantitative model evaluation, sensitivity analysis and extensive documentation please refer to [5].

Version information

MoBi Version 9.1

Code of conduct

Everyone interacting in the Open Systems Pharmacology community (codebases, issue trackers, chat rooms, mailing lists etc...) is expected to follow the Open Systems Pharmacology code of conduct.

Contribution

We encourage contribution to the Open Systems Pharmacology community. Before getting started please read the contribution guidelines. If you are contributing code, please be familiar with the coding standard.

License

The model code is distributed under the GPLv2 License.

Reference

[1] Berglund F, Killander J, Pompeius R. Effect of trimethoprim-sulfamethoxazole on the renal excretion of creatinine in man. The Journal of Urology. 1975;114(6):802-8.

[2] Herrera J, Avila E, Marín C, Rodríguez-Iturbe B. Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia. Nephrology Dialysis Transplantation. 2002;17(4):602-7.

[3] Larsson A, Akerstedt T, Hansson LO, Axelsson J. Circadian variability of cystatin C, creatinine, and glomerular filtration rate (GFR) in healthy men during normal sleep and after an acute shift of sleep. Chronobiology International. 2008;25(6):1047-61.

[4] Mayersohn M, Conrad KA, Achari R. The influence of a cooked meat meal on creatinine plasma concentration and creatinine clearance. British Journal of Clinical Pharmacology. 1983;15(2):227-30.

[5] Türk D, Müller F, Fromm MF, Selzer D, Dallmann R, Lehr T. Renal transporter-mediated drug-biomarker interactions of the endogenous substrates creatinine and N1 -methylnicotinamide: a PBPK modeling approach. Clinical Pharmacology & Therapeutics. 2022. Online ahead of print