Pharmacokinetic Modelling to Study the Biodistribution of Nanoparticles

Abstract

Pharmacokinetics is a key component of pharmacology and is an essential aspect during drug discovery and development phases that evaluates the safety and efficacy profiles. Mathematical models mainly physiologically based pharmacokinetic (PBPK) models have been increasingly used that can help in drug screening and identification; dose optimisation prior to preclinical and clinical trials using in vitro data, thus saving time and resources. PBPK models describe the pharmacokinetic processes – absorption, distribution, metabolism and elimination (ADME) using various mathematical correlations including in vitro – in vivo extrapolations in humans. Nanoparticles are been increasingly used for drug delivery due to their advantages over conventional formulations such as enhanced absorption, longer half-life, good safety and efficacy, targeted delivery etc. However, studies using nanoparticles in humans can be associated with various obstacles including ethical and logistical, hindering the drug development process. PBPK models overcome the earlier mentioned problems and can evaluate various biological and molecular processes that define drug pharmacokinetics using in vitro data. This chapter summarises the approach of PBPK models, its challenges and possibilities to assess the key ADME mechanisms involved during various mucosal routes of administration using several allometric, anthropometric and rate equations to inform drug pharmacokinetics in humans.