Related Experiment Video
Updated: Jun 18, 2025
08:28
Development of an In Vitro Ocular Platform to Test Contact Lenses
Published on: April 6, 2016
10.6K
Clinical Ocular Exposure Extrapolation for a Complex Ophthalmic Suspension Using Physiologically Based
Maxime Le Merdy1, Jessica Spires1, Ming-Liang Tan2
1Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA 93534, USA.
Pharmaceutics
|July 27, 2024
Summary
Developing generic ophthalmic drugs is complex. Ocular physiologically based pharmacokinetic (O-PBPK) models can predict drug exposure in the eye, aiding generic ophthalmic product development.
Area of Science:
- Ophthalmology
- Pharmacokinetics
- Drug Development
Background:
- Developing generic ophthalmic drugs with complex formulations presents significant challenges.
- The ocular system's complexity and limited testing methods hinder the evaluation of drug-physiological interactions.
- Ocular physiologically based pharmacokinetic (O-PBPK) models offer a solution for understanding drug distribution in inaccessible eye tissues.
Purpose of the Study:
- To demonstrate the utility of an O-PBPK model in predicting human ocular drug exposure.
- To utilize Besifloxacin (Bes) ophthalmic suspension as a case study for model validation.
- To assess the model's capability in predicting exposure from complex ophthalmic formulations.
Main Methods:
- An O-PBPK model was developed for Bes ophthalmic suspension, incorporating nasolacrimal drainage, particle dissolution, and ocular absorption/distribution.
- The model accounted for the effect of a controlled release formulation (Durasite®) on drug retention.
- Rabbit ocular data was used to validate the model, followed by adjustment of physiological parameters for human extrapolation.
Main Results:
- O-PBPK model simulations accurately described observed Bes concentrations in rabbit eye tissues.
- The model successfully predicted Bes exposure in the human eye after topical administration.
- Extrapolation to human ocular exposure was achieved by adjusting physiological parameters.
Conclusions:
- O-PBPK models are valuable tools for predicting drug exposure in the eye for ophthalmic generic drug development.
- This study validates the use of O-PBPK modeling for complex ophthalmic suspensions.
- The developed model facilitates regulatory assessment and development of generic ophthalmic products.
Related Concept Videos
01:26Pharmacokinetic Models: Comparison and Selection Criterion
64
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
64
01:20Pharmacokinetic Models: Overview
635
Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
635
01:19One-Compartment Open Model for IV Bolus Administration: General Considerations
178
The one-compartment model is a pharmacokinetic tool that models the body as a single, uniform compartment, facilitating the understanding of drug distribution and elimination. This model is particularly beneficial for intravenous (IV) bolus administration, where the drug rapidly circulates throughout the body.
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
178
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
36
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
36
01:17Clearance Models: Noncompartmental Models
53
Clearance is a pharmacokinetic parameter traditionally defined by compartment models, signifying the rate at which a drug is expelled from the body. However, a noncompartmental model offers an alternative method for assessing clearance, primarily employing empirical data obtained after administering a single drug dose.
The noncompartmental approach capitalizes on extensive sampling data, correlating the volume of distribution to systemic exposure and the administered dosage. This method enables...
The noncompartmental approach capitalizes on extensive sampling data, correlating the volume of distribution to systemic exposure and the administered dosage. This method enables...
53
01:12One-Compartment Open Model for Extravascular Administration: Zero-Order Absorption Model
73
Extravascular administration, such as oral or intramuscular routes, is a non-invasive drug delivery method, often preferred for ease and patient compliance. A key factor here is absorption, which dictates how quickly and effectively the drug enters the bloodstream from the administration site. Absorption follows either zero-order or first-order kinetics.
Zero-order absorption maintains a steady rate irrespective of the amount of drug left to be absorbed, making it a constant process. In the...
Zero-order absorption maintains a steady rate irrespective of the amount of drug left to be absorbed, making it a constant process. In the...
73