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System-based Approach to Prediction of Surfactants’ Influences on Pharmaco-kinetics and Pharmacodynamics

Systemorientierter Ansatz zur Vorhersage des Einflusses von Tensiden auf die Pharmakokinetik und Pharmakodynamik
Zuzana Vitková, Marián Tárník, Eva Miklovičová, Ján Murgaš, Jarmila Oremusová and Anton Vitko

Abstract

The paper presents a system-based approach for predicting the changes of the plasma concentration and the therapeutic effect of sodium p-aminosalicylate caused by addition of surfactant Tween 80 to a liquid dosage form. A predictive pharmacokinetic model of the oral administration is synthetized together with the corresponding model of its parametric sensitivity. The sensitivities predicted by the model are then compared to those obtained from the in-vi vo experiment. The close correspondence between them is used to prove the model correctness. Similarly the Emax model of the therapeutic effect predicts influences of the added surfactants on the therapeutic effect. In this context, the problem of determining an optimal absorption rate for the desired time course of the therapeutic effect is solved. As a by-product this study, it is shown that the (in-silico generated) sensitivity of plasma concentration to the drug absorption rate may provide information on how far the in-silico experiment can serve as a substitute for in-vivo bioavailability and bioequivalence studies

Kurzfassung

Der Beitrag stellt einen systembasierten Ansatz zur Vorhersage der Änderungen der Plasmakon zentration und der therapeutischen Wirkung von Natrium-p-aminosalicyla t vor, die durch die Zugabe des Tensids Tween 80 zu einer flüssigen Dosierungsform verursacht werden. Ein prädiktives pharmakokinetisches Modell der oralen Verabreichung wird zusammen mit dem entsprechenden Modell seiner parametrischen Empfindlichkeit erstellt. Die vom Modell vorhergesagten Empfindlichkeiten werden dann mit denen aus dem in-vivo-Experiment verglichen. Die enge Übereinstimmung zwischen ihnen wird verwendet, um die Modellkorrektheit zu beweisen. In ähnlicher Weise sagt das Emax-Modell der therapeutischen Wirkung Einflüsse der zugegebenen Tenside auf die therapeutische Wirkung voraus. In diesem Zusammen hang wird das Problem, die optimale Resorptionsrate für den gewünsc hten zeitlichen Verlauf der therapeutischen Wirkung zu ermitteln, gelöst. Als Nebenprodukt dieser Studie wird gezeigt, dass die (in-silico erzeugte) Empfindlichkeit der Plasmakonzentration gegenüber der Arzneimittelabsorptionsrate Aufschluss darüber geben kann, inwieweit das in-silico-Experiment als Ersatz für Studien der in vivo-Bioverfügbarkeit und Bioäquivalenz dienen kann.


Correspondence address, Mr. Marián Tárník, Institute of Robotics and Cybernetics, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovičova 3, 81231 Bratislava, Slovak Republic, E-Mail:

Assoc. Prof. Dr. rer. nat. Zuzana Vitková, PhD. graduated from the Faculty of Pharmacy of the Comenius University in Bratislava, where she has been acting as a teacher and researcher. Research: Drug delivery, bio-pharmacy, pharmacokinetics, pharmacodynamics

Eng. Marian Tárník, PhD. graduated from the Faculty of Electrical Engineering and Information Technology of the Slovak University of Technology in Bratislava. Research: Theory of automatic control, bio-cybernetics, intelligent systems

Prof. Eng. Ján Murgaš, PhD. graduated from the Faculty of Electrical Engineering and Information Technology of the Slovak University of Technology in Bratislava. Research: Theory of automatic control, intelligent systems and bio-cybernetics.

Assoc. Prof. Eng. Eva Miklovičová, PhD. graduated from the Faculty of Electrical Engineering and Information Technology of the Slovak University of Technology in Bratislava. Research: Theory of automatic control, system simulation, bio-cybernetics.

Eng. Jarmila Oremusová, PhD. graduated from the Faculty of Chemical Technology of the Slovak University of Technology in Bratislava. Research: Physical-chemical analysis of drugs.

Prof. Eng. Anton Vitko, PhD. graduated from the Faculty of Electrical Engineering and Information Technolo gy of the Slovak University of Technology in Bratislava. Research: Robotics, bio-cybernetics, system theory.


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Received: 2019-03-12
Accepted: 2019-05-20
Published Online: 2020-01-23
Published in Print: 2020-01-21

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