alexa System approach to modeling metabolite formation from parent drug: a working example with methotrexate.
Toxicology

Toxicology

Journal of Drug Metabolism & Toxicology

Author(s): Dedk L, Durisov M

Abstract Share this page

Abstract The aim of this methodological study was to present and exemplify a system-approach-based technology in modeling the formation of the metabolite from the parent drug. To represent this process, the parent-metabolite dynamic system was defined in such a way that the concentration-time profile of the parent drug was considered the input, while the concentration-time profile of the metabolite the output, of this system. The system-approach-based modeling technology was used to determine the model of the parent-metabolite dynamic system and to obtain the model-based estimates of the rate of metabolite formation, the rate of metabolic ratio and the mean time of metabolite formation. The technology was applied to concentration data for methotrexate and 7-hydroxymethotrexate in patients with psoriasis after a single oral methotrexate dose. Third-order linear models were selected as optimal to approximate the parent-metabolite dynamic systems representing the formation of 7-hydroxymethotrexate from methotrexate of these patients. The model-based estimates of the metabolic ratios ranged from 0.53 to 0.95. The model-based estimates of the mean times of formation of 7-hydroxymethotrexate from methotrexate ranged from 9.13 to 25.13 h. The model-based estimates of the rates of formation of 7-hydroxymethotrexate from methotrexate reached peak values (ranging from 0.03 to 0.11 h-1) in the time interval 1.5-4.5 h after administration of methotraxate. This study does not only introduce the method that may be useful in gaining insight into metabolite formation, but also presents a new example of the methodological, conceptual and computational uniformity of the system-approach-based technology in modeling various biomedical systems.
This article was published in Methods Find Exp Clin Pharmacol and referenced in Journal of Drug Metabolism & Toxicology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords