Original scientific paper

https://doi.org/10.5599/admet.625

Physiologically-based pharmacokinetic simulations in pharmacotherapy: selection of the optimal administration route for exogenous melatonin

Adriana Savoca ; PSE-Lab, Process Systems Engineering Laboratory, Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy
Davide Manca ; PSE-Lab, Process Systems Engineering Laboratory, Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy

Abstract

The benefits of melatonin on human body are drawing increasing attention from several researchers in different fields. While its role as cure for sleep disturbances (e.g., jet lag, insomnia) is well documented and established, new functions in physiological and pathophysiological processes are emerging. To investigate these effects, there is need for the characterization of melatonin transport processes in the body and resulting pharmacokinetics. Although recent works propose physiologically-based pharmacokinetic modelling of melatonin, no work has yet highlighted the potential of PBPK simulations to shed light on melatonin pharmacokinetic aspects and discrimination among administration routes. This paper presents, validates, and discusses a versatile PBPK model featuring different ways of administration and compares the resulting pharmacokinetic profiles of intravenous, oral, and transdermal administration, with the goal of understanding which is the optimal route to achieve either physiological and/or supraphysiological melatonin levels.

Keywords

Melatonin; PBPK; administration route; transdermal; controlled release; simulation; clinical efficacy

Hrčak ID:

217378

URI

https://hrcak.srce.hr/217378

Publication date:

23.2.2019.

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