Incidence and nature of testicular toxicity findings in pharmaceutical development
| Autor: | Jennifer C. Sasaki, Monica Seger, James H. Kim, Louise Parks Saldutti, Robert E. Chapin, Brian P. Enright, Keith Jarvi, David Gregory Hall, Mary L. Hixon, Jeffrey S. Moffit, William J. Breslin, Terri Mitchard |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Embryology medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Health Toxicology and Mutagenesis Drug Evaluation Preclinical MEDLINE Pharmacology Toxicology Testis Toxicity Tests medicine Animals Humans Intensive care medicine business.industry Incidence (epidemiology) Confounding Omics Clinical trial Pharmaceutical Preparations Drug development Drug Design Biomarker (medicine) Testicular toxicity business Developmental Biology |
| Zdroj: | Birth Defects Research Part B: Developmental and Reproductive Toxicology. 92:511-525 |
| ISSN: | 1542-9733 |
| DOI: | 10.1002/bdrb.20338 |
| Popis: | BACKGROUND: Testicular toxicity (TT) is a sporadic and challenging issue in pharmaceutical drug development. Efforts to develop TT screening assays or biomarkers have been overshadowed by consortium efforts to predict drug-induced toxicities such as hepatic injury, which are encountered more frequently. METHODS: To gauge the current state of the field and to prioritize future TT activities, the International Life Sciences Institute-Health and Environmental Sciences Institute Developmental and Reproductive Toxicology (DART) Technical Committee sponsored a survey to better understand the incidence and nature of TT findings encountered during drug development. RESULTS: Highlights from the 16 survey respondents include: (1) Although preclinical TT was encountered relatively infrequently, half of the participants observed repeated problems with TT during pharmaceutical development, (2) despite control measures such as use of sexually mature animals to diminish confounding effects of spurious lesions, interpretation of TT remains a challenge, (3) “traditional” evaluation tools such as hormonal monitoring and newer approaches such as -omics are utilized to investigate testicular changes, and (4) an understanding of the risk and relevance of TT findings is achieved through joint consideration of factors such as species specificity, potential mode of action, and safety margins. CONCLUSIONS: TT remains a relatively uncommon but persistent challenge in pharmaceutical development. Although current preclinical TT approaches appear to be effective in limiting the occurrence of pharmaceutical candidate attrition in clinical trials, improved biomarker or screening platforms would allow companies to identify TT at an earlier stage, thus decreasing the time and resources expended on safety evaluation of pharmaceutical candidates. Birth Defects Res (Part B) 92: 511–525, 2011. © 2011 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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