Clinical pharmacokinetic study of latrepirdine via in silico sublingual administration.

In recent decades, numerous in silico methodologies have been developed focused on the study of pharmacodynamic, pharmacokinetics and toxicological properties of drugs. The study of the pharmacokinetic behavior of new chemical entities is an essential part of the successful development of a new drug and Gastroplus™ is a simulation software used to predict the pharmacokinetic behavior of chemical entities. Latrepirdine is a drug that has been studied for Alzheimer's disease and Huntington's disease and later abandoned by the pharmaceutical industry already in the clinical trials because it has not demonstrated therapeutic efficacy. During this project, through Gastroplus™ simulations, it was possible to achieve predicted values of C_max coincident with those found in clinical trials, showing its utility in the prediction of pharmacokinetic parameters. Besides, sublingual delivery has the potential to offer improved bioavailability by circumventing first-pass metabolism. This study used GastroPlus™ to simulate sublingual administration of latrepirdine and the results showed improvements in bioavailability and plasma concentrations achieved though this route of administration.