A physiologically based pharmacokinetic model of metoclopramide after i.v. administration to healthy volunteers and evaluation of linear dose predictability

Title

Oral presentation

Description

Hristo Petkov, Kristina Bozhinova, Anton Filipov, Tsveta Sarafska, Ivanka Atanasova, Dimiter Terziivanov
Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski ”, Bulgaria

Subject

PBPK modelling is a scientific tool in applied pharmacokinetics (PK) and toxicokinetics. The main merit of PBPK is it’s ability to predict not only drug plasma concentrations, as it does the classical PK and Population PK, but also to predict drug concentrations in different body organs and tissues. Dose linearity is a fundamental concept in PK model building and is the scientific basis of modern drug therapy . The approved way is to increase drug doses and to calculate the generated AUCs by each of the doses and thereafter to look for dose (non-) linearity. Aim: To build up PBPK model of MCP after I.V. administration to healthy male volunteers using the PBPK modelling software PKQuest and to assess its ability to predict dose-concentrations linearity. Data were used from 6 randomly selected healthy male volunteers who were treated with an intravenous bolus injection containing Reglan sol. injection 5 mg/ml. Conclusions: The PBPK model of MCP is sensitive enough to discern doses with different sizes. MCP PK behaviour after I.V. administration is linear within the selected dose range. Dose-linearity can be used for internal validation of PBPK models as well as for predictive purposes.
The work is part of a research project: "Physiologic based pharmacokinetic modelling application in assessment pharmacokinetics of different medicinal forms of metoclopramide", funded by the Faculty of Chemistry and Pharmacy, SU St. Kl. Ohridski.
Keywords: Physiologically based pharmacokinetic modelling, metoclopramide