Is 1-Methylnicotinamide a Good Organic Cation Transporter 2 (OCT2) Biomarker?

The impact of potential precipitant drugs on plasma or urinary exposure of endogenous biomarkers is emerging as an alternative approach to evaluating drug-drug interaction (DDI) liability. 1-Methylnicotinamide (NMN) has been proposed as a potential biomarker for renal organic cation transporter 2 (OCT2). NMN is synthesized in the liver from nicotinamide by nicotinamide N-methyltransferase (NNMT) and is subsequently metabolized by aldehyde oxidase (AO).

Power of integrating PBPK with PBBM (PBPK-BM): a single model predicting food effect, gender impact, drug-drug interactions and bioequivalence in fasting & fed conditions.

Over the past few years, PBPK and PBBM modelling have proven their significance in drug development. PBPK modelling is traditionally used to predict drug-drug interactions, exposures in special populations whereas PBBM modelling is a part of PBPK modelling that is used for a range of biopharmaceutics applications.Because of these differences in utilities, often PBPK and PBBM models are developed separately.

Predicting transporter mediated drug-drug interactions via static and dynamic physiologically based pharmacokinetic modeling: A comprehensive insight on where we are now and the way forward.

The greater utilization and acceptance of physiologically-based pharmacokinetic (PBPK) modeling to evaluate the potential metabolic drug-drug interactions is evident by the plethora of literature, guidance's, and regulatory dossiers available in the literature. In contrast, it is not widely used to predict transporter-mediated DDI (tDDI). This is attributed to the unavailability of accurate transporter tissue expression levels, the absence of accurate in vitro to in vivo extrapolations (IVIVE), enzyme-transporter interplay, and a lack of specific probe substrates.