The non-GLP toleration/dose range finding study: design and methodology used in an early toxicology screening program.
Proc West Pharmacol Soc
; 52: 94-8, 2009.
Article
en En
| MEDLINE
| ID: mdl-22128433
A major directive of Pharmaceutical Research and Development (R&D) is to efficiently advance potential new chemical entities (NCEs) from the Discovery therapeutic area into Global Preclinical Development (GPCD), where a safety profile can be established. To facilitate the transition a comprehensive toxicity evaluation is required. In order to support both the R&D Discovery teams and GPCD, investigative (non-GLP) tolerance/dose range finding studies are conducted. These studies are designed to provide a quality toxicological and toxicokinetic assessment of potential NCEs early in the drug development process. During tolerance evaluations, compounds are first assessed in a single dose escalation (SDE) phase where rodents (or canines) receive a single dose anticipated to achieve relevant multiples of the efficacious dose. Data from this phase evaluates NCE absorption, and assists in estimating the maximum tolerated dose for a single administration and establish doses for a repeat dose (RD) phase. Data from the RD phase are used to determine potential target tissues of toxicity and also select doses for future GLP Toxicology studies. Thus, a rapid assessment of the toxicological profile of the NCE can be made to establish initial safety facilitating conduct of subsequent regulatory Toxicological studies and potentially earlier entry into clinical trials.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proyectos de Investigación
/
Pruebas de Toxicidad
Tipo de estudio:
Diagnostic_studies
/
Guideline
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Proc West Pharmacol Soc
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos