Target organ toxicities in studies conducted to support first time in man dosing: An analysis across species and therapy areas
| Autor: | Katie Stamp, Steve Horner, R.D. Callander, Ruth Roberts, David Ryan, Sally Robinson |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Central Nervous System
Male Pathology medicine.medical_specialty Rodent Drug Evaluation Preclinical Physiology Spleen Inflammation Genitalia Male Toxicology Risk Assessment Species Specificity Animals Laboratory biology.animal Toxicity Tests medicine Animals Humans Dosing Respiratory system Kidney biology Drugs Investigational General Medicine medicine.anatomical_structure Liver Toxicity Female Bone marrow Chemical and Drug Induced Liver Injury medicine.symptom |
| Zdroj: | Regulatory Toxicology and Pharmacology. 65:334-343 |
| ISSN: | 0273-2300 |
| DOI: | 10.1016/j.yrtph.2013.02.002 |
| Popis: | An analysis of target organ toxicities in first time in man (FTiM) toxicity studies for 77 AstraZeneca candidate drugs (CDs) was conducted across a range of therapy areas. In the rodent, the most frequently affected organ was the liver followed by adrenal glands, kidney, spleen, bone marrow and thymus. In non-rodent, liver and thymus were the most frequently affected organs, followed closely by the testis and GI tract. The profile of affected organs was largely similar across the therapy areas of respiratory and inflammation, cardiovascular/gastrointestinal and CNS/pain. The oncology/infection therapy area differed with a larger range of organs affected. For the 75 CDs for which both rodent and non-rodent studies were conducted, new target organs were identified in non-rodents for 43 of the CDs. Notably, the changes seen only in non-rodents included organ systems of high relevance for human risk assessment such as the liver, male reproductive tissues and CNS. Additionally, profiles were similar for those CDs that progressed into human trials and those that did not. Overall, our data provide new insights into drug toxicity profiles in pre-clinical species and additionally confirm the value of using non-rodents as a second species in toxicity testing to support human safety. |
| Databáze: | OpenAIRE |
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