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Clinical Ocular Exposure Extrapolation for Ophthalmic Solutions Using PBPK Modeling and Simulation.
Maxime Le Merdy1, Farah AlQaraghuli2, Ming-Liang Tan3
1Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA, 93534, USA. maxime.lemerdy@simulations-plus.com.
Pharmaceutical Research
|September 23, 2022
Summary
This study validates using ocular physiologically based pharmacokinetic (PBPK) models to predict human drug exposure from rabbit data, aiding generic ophthalmic product development.
Area of Science:
- Pharmacokinetics
- Ocular Drug Delivery
- Translational Science
Background:
- Developing generic ophthalmic drugs is complex due to the eye's physiology and limited human testing.
- Rabbit models offer more accessible in vivo ocular drug concentration data than human studies.
Purpose of the Study:
- To demonstrate the utility of an ocular physiologically based pharmacokinetic (PBPK) model.
- To enable translation of ocular exposure data from rabbit to human subjects.
Main Methods:
- Utilized the Ocular Compartmental Absorption and Transit (OCAT™) model within GastroPlus®.
- Developed PBPK models for levofloxacin, moxifloxacin, and gatifloxacin ophthalmic solutions in rabbit eyes.
- Scaled physiological parameters for human ocular physiology to predict human exposure.
Main Results:
- OCAT model simulations accurately described rabbit ocular concentrations for three fluoroquinolones.
- The PBPK models successfully predicted human ocular exposure following various administration routes and schedules.
Conclusions:
- The study validates an extrapolation method for predicting human ocular exposure using PBPK models.
- Further case studies are needed to confirm the PBPK model's utility across diverse ophthalmic APIs and formulations.
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