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Clinical Ocular Exposure Extrapolation for an Ophthalmic Ointment Using PBPK Modeling and Simulation
Maxime Le Merdy1, Ming-Liang Tan2, Viera Lukacova3
1Simulations Plus, Inc., PO Box 12317, Research Triangle Park, North Carolina, 27709, USA. maxime.lemerdy@simulations-plus.com.
The AAPS Journal
|October 1, 2025
Summary
Ocular physiologically based pharmacokinetic (PBPK) models can predict drug exposure in the human eye. This study validated an ocular PBPK model for ofloxacin ointment, showing accurate preclinical to clinical extrapolation for ophthalmic drug development.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Ocular Drug Delivery
- Computational Modeling
Background:
- Generic ophthalmic drug development requires efficient bioequivalence (BE) assessment.
- Ocular physiologically based pharmacokinetic (PBPK) models offer non-invasive insights into drug distribution within eye tissues.
- Previous work validated ocular PBPK models for translating rabbit to human exposure for solutions and suspensions.
Purpose of the Study:
- To demonstrate the utility of an ocular PBPK model for predicting human exposure to ophthalmic ointments.
- To present ofloxacin (OFL) ointment as a case study for ocular PBPK modeling.
- To assess the predictive capability of the Ocular Compartmental Absorption and Transit (OCAT™) model for ophthalmic ointments.
Main Methods:
- Developed an ocular PBPK model for OFL solution and ointment using the OCAT™ model in GastroPlus®.
- Incorporated OFL release kinetics, ointment application time, and ocular absorption/distribution parameters for rabbit eyes.
- Adjusted physiological parameters to simulate human ocular physiology and predicted human exposure.
Main Results:
- The OCAT™ model accurately described observed aqueous humor concentrations in rabbits for both OFL solution and ointment.
- Ointment formulation parameters (Higuchi release rate, application time) were fitted to match rabbit data.
- Predicted human aqueous humor concentrations for OFL solution and ointment were within the range of observed values.
Conclusions:
- The validated ocular PBPK model demonstrates successful preclinical to clinical extrapolation for ofloxacin ointment.
- This approach supports the use of ocular PBPK models for predicting human exposure to ophthalmic ointments.
- Further case studies are needed to confirm the generalizability of these findings for other ophthalmic ointment products.
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