N1-Methylnicotinamide (NMN)-Model

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

Repository files

Within this repository, we distribute a whole-body PBPK model of NMN, 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 liver cells, metabolism via AOX1, active tubular secretion via OCT2 and MATE1, active tubular reabsorption as well as diurnal variation.

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

Version information

MoBi Version 9.1

Code of conduct

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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] Musfeld C, Biollaz J, Bélaz N, Kesselring UW, Decosterd LA. Validation of an HPLC method for the determination of urinary and plasma levels of N1-methylnicotinamide, an endogenous marker of renal cationic transport and plasma flow. Journal of Pharmaceutical and Biomedical Analysis. 2001;24(3):391-404.

[2] Okamoto H, Ishikawa A, Yoshitake Y, Kodama N, Nishimuta M, Fukuwatari T, Shibata K. Diurnal variations in human urinary excretion of nicotinamide catabolites: effects of stress on the metabolism of nicotinamide. American Journal of Clinical Nutrition. 2003;77(2):406-10.

[3] Weber W, Toussaint S, Looby M, Nitz M, Kewitz H. System analysis in multiple dose kinetics: evidence for saturable tubular reabsorption of the organic cation N1-methylnicotinamide in humans. Journal of Pharmacokinetics and Biopharmaceutics. 1991;19(5):553-74.

[4] 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