Advancing Ophthalmic Drug Development: Challenges and Strategies

There are a large number of patients suffering from ocular disease and visual impairments. Uncorrected refractive errors (e.g., myopia or hyperopia), cataracts, and AMD are the main causes of moderate to severe visual impairments or blindness, which substantially affect patient quality of life. This blog discusses the challenges and strategies for PK studies in ophthalmology.

Ocular drug delivery

The eye is divided into the anterior and posterior segments with the lens as the boundary. The biggest challenge in ocular drug delivery research is overcoming static and dynamic biological barriers to effectively deliver the drug to target ocular tissues. These barriers are generally categorized as anterior segment barriers and posterior segment barriers.¹

The clarification of the anterior and posterior segments of the eye plays a crucial role in studying the distribution and delivery of ophthalmic drugs. Routes for ocular drug delivery can be broadly classified into systemic and topical administration.

• Systemic administration involves oral administration, intravenous injection, or intramuscular injection. However, due to factors such as the blood–eye barrier, the amount of drug reaching the target tissues by systemic administration is limited, which leads to inadequate therapeutic effects.

• For ophthalmic drugs, topical drug delivery is primarily used in clinical studies. Topical ocular drug delivery is classified into three main categories: topical administration on the ocular surface, intraocular administration, and periocular administration.

What are strategies for ophthalmic preclinical PK studies?

1. Selection of animal species: A single animal model could not be used to fully simulate the drug efficacy in the human body. Therefore, it is recommended to use a combination of multiple animal models for preclinical studies to comprehensively evaluate drug properties.

2. PK study models: Appropriate multi-compartment models are conducive to topical ocular PK studies. However, data modeling of this approach is based on different assumptions and is relatively complex and mathematically intricate. Notably, improper use of this method may affect the accuracy of the data. In preclinical studies, non-compartment models are more often used to calculate ophthalmic parameters.

3. For drugs using topical drug delivery (e.g., intravitreal injection administration), both topical and systemic exposure should be assessed.

4. For drugs with systemic exposure or those administered through systemic administration, conventional systemic PK studies can be applied to assess systemic exposure and PK profiles such as drug distribution, metabolism, and elimination.

5. For drugs distributed mainly in the ocular tissues and exerting drug efficacy within the eye, topical ocular PK evaluation should be performed, including the distribution, metabolism, and elimination processes of the drug in ocular tissues. Additionally, the distribution and target binding of drugs should be studied.

What you need to know about ophthalmic research challenges

The challenges of DMPK preclinical studies in ophthalmology include:

1. The high demand for high-level animal experimental skills due to the delicate eye structures and the need for professional veterinary and anatomical teams to perform drug administration and ocular tissue collection

2. The difficulty in ophthalmic sample bioanalysis is due to various ophthalmic collection matrices and the large number of samples, often in small volumes, with high sample handling requirements.

If you want to learn more details about the challenges and strategy of ophthalmic drug development, please read the article now.

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