Models and Approaches Describing the Metabolism, Transport, and Toxicity of Drugs Administered by the Ocular Route.
Drug Metab Dispos
; 46(11): 1670-1683, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30111625
ABSTRACT
The eye is a complex organ with a series of anatomic barriers that provide protection from physical and chemical injury while maintaining homeostasis and function. The physiology of the eye is multifaceted, with dynamic flows and clearance mechanisms. This review highlights that in vitro ocular transport and metabolism models are confined by the availability of clinically relevant absorption, distribution, metabolism, and excretion (ADME) data. In vitro ocular transport models used for pharmacology and toxicity poorly predict ocular exposure. Although ocular cell lines cannot replicate in vivo conditions, these models can help rank-order new chemical entities in discovery. Historic ocular metabolism of small molecules was assumed to be inconsequential or assessed using authentic standards. While various in vitro models have been cited, no single system is perfect, and many must be used in combination. Several studies document the use of laboratory animals for the prediction of ocular pharmacokinetics in humans. This review focuses on the use of human-relevant and human-derived models which can be utilized in discovery and development to understand ocular disposition of new chemical entities. The benefits and caveats of each model are discussed. Furthermore, ADME case studies are summarized retrospectively and capture the ADME data collected for health authorities in the absence of definitive guidelines. Finally, we discuss the novel technologies and a hypothesis-driven ocular drug classification system to provide a holistic perspective on the ADME properties of drugs administered by the ocular route.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Ojo
/
Bibliotecas de Moléculas Pequeñas
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Drug Metab Dispos
Asunto de la revista:
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article