Speaker
Description
In the space environment, changes in factors such as blood circulation under microgravity conditions can potentially result in modifications to the pharmacokinetic aspects of drug utilization, impacting drug absorption, distribution, metabolism, and excretion within the body. Nevertheless, assessing these alterations in a terrestrial setting can be challenging. Thus, there is a need for discussion regarding the use of mathematical models to predict and comprehend these changes. The objective of this study is to create gastrointestinal pharmacokinetic models in order to formulate a new agent for assessing related pharmacodynamics. This is done to control diseases, alleviate patient symptoms, and expedite disease resolution.
In this study, both compartment-based pharmacokinetic models (specifically a two-compartment model) and physiologically based pharmacokinetic models (restricted to gastrointestinal fluid rates) were employed to characterize the gastrointestinal pharmacokinetics of new agents and to simulate profiles for evaluating their effects at the target site. This mathematical model was established in both animal and human models and proved to be beneficial in nonclinical and clinical phases of drug development. The absorption kinetics (ka, absorption rate constant) of therapeutic drugs in the gastrointestinal tract were considered as the elimination kinetics (kel, elimination rate constant) in these models. The kel value was determined or estimated through in vivo animal pharmacokinetic studies, in vitro cell systems, or in-silico methods. The permeabilities of model compounds, ranging from 0.12 to 15.6 cm/sec, were obtained using the Caco2 cell system, which was used to estimate the ka values. The gastrointestinal fluid rates in animals and humans, as previously reported, were applied in this study. The Michaelis-Menten kinetic model or an indirect model was employed in the proposed pharmacokinetic model, depending on the characteristics of the therapeutic agent.
In conclusion, this study established a combined mathematical model incorporating compartment-based and physiologically based pharmacokinetic elements. This model can be a valuable tool for evaluating the behavior of therapeutic agents and understanding the pharmacodynamics of new drugs in a space environment.
