Phospholipogenic Pharmaceuticals Are Associated with a Higher Incidence of Histological Findings than Nonphospholipogenic Pharmaceuticals in Preclinical Toxicology Studies
Joint Authors
Boyer, Scott
Damewood, James R.
Ciaccio, Paul J.
Barone, Linda R.
Fikes, James
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-14
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Pharmacy, Health & Medical Sciences
Medicine
Abstract EN
While phospholipidosis is thought to be an adaptive response to chemical challenge, many phospholipogenic compounds are known to display adverse effects in preclinical species and humans.
To investigate the link between phospholipogenic administration and incidence of preclinical histological signals, an internal AstraZeneca in vivo toxicology report database was searched to identify phospholipogenic and nonphospholipogenic compounds.
The datasets assembled comprised 46 phospholipogenic and 62 nonphospholipogenic compounds.
The phospholipogenic potential of these compounds was confirmed by a pathologist's interpretation and was supported by well-validated in silico and in vitro models.
The phospholipogenic dataset contained 37 bases, 4 neutral compounds, 3 zwitterions, and 1 acid, whereas the nonphospholipogenic dataset contained 9 bases, 34 neutrals, 1 zwitterion, and 18 acids.
Histologic findings were tracked for adrenal gland; bone marrow; kidney; liver; lung; lymph node; spleen; thymus; and reproductive organs.
On average, plasma exposures were higher in animals dosed with the nonphospholipogenics.
Phospholipogenics yielded proportionally more histologic changes (exclusive of phospholipidosis itself) in all organs.
Statistically significant higher frequencies of liver necrosis, alveolitis/pneumonitis, as well as lymphocytolysis in the thymus, lymph nodes, and spleen occurred in response to phospholipogenics compared to that for nonphospholipogenics.
American Psychological Association (APA)
Barone, Linda R.& Boyer, Scott& Damewood, James R.& Fikes, James& Ciaccio, Paul J.. 2012. Phospholipogenic Pharmaceuticals Are Associated with a Higher Incidence of Histological Findings than Nonphospholipogenic Pharmaceuticals in Preclinical Toxicology Studies. Journal of Toxicology،Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-462283
Modern Language Association (MLA)
Barone, Linda R.…[et al.]. Phospholipogenic Pharmaceuticals Are Associated with a Higher Incidence of Histological Findings than Nonphospholipogenic Pharmaceuticals in Preclinical Toxicology Studies. Journal of Toxicology No. 2012 (2012), pp.1-7.
https://search.emarefa.net/detail/BIM-462283
American Medical Association (AMA)
Barone, Linda R.& Boyer, Scott& Damewood, James R.& Fikes, James& Ciaccio, Paul J.. Phospholipogenic Pharmaceuticals Are Associated with a Higher Incidence of Histological Findings than Nonphospholipogenic Pharmaceuticals in Preclinical Toxicology Studies. Journal of Toxicology. 2012. Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-462283
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-462283