Blood retinal barrier and ocular pharmacokinetics: Considerations for the development of oncology drugs

Area of Science:

• Oncology
• Pharmacology
• Ophthalmology

Background:

• Tyrosine kinase inhibitors (TKIs) are targeted cancer therapies with less understood toxicity profiles.
• Ocular adverse events are common toxicities associated with TKIs.
• Mer receptor tyrosine kinase (MERTK) inhibition shows promise for cancer immunotherapy but faces challenges due to ocular MERTK expression.

Purpose of the Study:

• To review pharmacokinetic (PK) parameters and in vitro absorption, distribution, metabolism, and excretion (ADME) assays for evaluating ocular disposition of TKIs.
• To assess the relationship between clinical PK and ocular adverse events for TKIs.
• To facilitate back-translation of findings to preclinical models for improved drug development.

Main Methods:

• Review of existing literature on TKI pharmacokinetics.
• Analysis of in vitro ADME assays relevant to ocular disposition.
• Correlation of clinical PK data with reported ocular adverse events.

Main Results:

• Ocular adverse events are a significant concern with TKIs.
• Understanding ocular disposition is key to mitigating TKI-induced ocular toxicity.
• PK and ADME data are essential for predicting and managing ocular safety.

Conclusions:

• Developing safe and effective oncology drugs requires a thorough understanding of ocular disposition.
• Integrating PK and safety assessments is vital for minimizing ocular toxicity in TKI therapy.
• Further research into ocular PK/ADME is needed for next-generation targeted cancer therapies.