Journal
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume 11, Issue 1, Pages 95-109Publisher
INFORMA HEALTHCARE
DOI: 10.1517/17425255.2015.980813
Keywords
AChE reactivators; biodistribution; biopharmaceutical classifications; organophosphorus intoxication; oximes; pharmacokinetics
Funding
- Romanian Ministry of National Education, CNCS-UEFISCDI project [PN-II-ID-PCE-2012-4-0651]
Ask authors/readers for more resources
Introduction: The therapeutic outcome of oximes used as reactivators of phosphorylated human acetylcholinesterase (AChE) is influenced, among other factors, by their biological distribution, their in vivo ability to achieve the nucleophilic attack and their affinity for the anionic center of the intact/inhibited AChE. Areas covered: An in silico evaluation of the molecular descriptors and biopharmaceutical properties of 454 set of oximes has been achieved. The available pharmacokinetic (PK) data was analyzed, in an attempt to illustrate their common characteristics and particularities. Based on the observed high water solubility and low permeability across biological barriers, we applied the officially adopted classification systems based on biopharmaceutical properties to identify the existing biopharmaceutical differences between the various oxime entities and to predict their in vivo fate. Expert opinion: The structural differences of the organophosphorus compounds (OP) and the available oximes reactivators of OP-inhibited AChE generate distinct toxicokinetic or PK profiles. The tissue compartment specific distribution is one of the key elements for assessment of reactivating efficiency. The distribution through highly specialized barriers, such as blood-brain barrier remains a considerable challenge. The high solubility - low permeability biopharmaceutical profile of oximes can be used to suggest the possible involvement of active transport systems.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available