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Updated: Jun 11, 2026
10:02
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Interaction between topically and systemically coadministered P-glycoprotein substrates/inhibitors: effect on vitreal
Ketan Hippalgaonkar1, Ramesh Srirangam, Bharathi Avula
1Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Summary
Topical P-glycoprotein (P-gp) inhibitors alter the eye
Area of Science:
- Ocular pharmacokinetics
- Drug transport mechanisms
- Ophthalmology
Background:
- P-glycoprotein (P-gp) plays a crucial role in drug efflux at the blood-retinal barrier.
- Understanding P-gp interactions is vital for optimizing ocular drug delivery and efficacy.
- Systemic drug administration faces challenges in achieving therapeutic concentrations in the vitreous humor.
Purpose of the Study:
- To investigate how topical P-glycoprotein (P-gp) substrates/inhibitors affect the vitreal pharmacokinetics of systemically administered P-gp substrates.
- To determine if coadministration of topical agents modulates the ocular disposition of systemically delivered drugs.
- To elucidate the role of P-gp in the retinal pigmented epithelium in drug kinetics.
Main Methods:
- Systemic intravenous administration of quinidine (a P-gp substrate) in anesthetized rabbits.
- Determination of quinidine concentration-time profiles in the vitreous humor.
- Coadministration of topical verapamil, prednisolone sodium phosphate (PP), and erythromycin.
- Comparison of vitreal pharmacokinetic parameters between control and treatment groups.
Main Results:
- Topical verapamil significantly altered quinidine's vitreal elimination rate, clearance, and AUC.
- Topical prednisolone sodium phosphate (PP) decreased vitreal elimination and increased AUC of quinidine.
- Erythromycin also showed statistically significant differences in vitreal profiles compared to control.
- Systemic plasma concentrations of quinidine remained unchanged, confirming localized ocular effects.
Conclusions:
- Topical P-gp modulators interact with systemically administered P-gp substrates.
- This interaction likely occurs via P-gp modulation on the retinal pigmented epithelium's basolateral membrane.
- Topical coadministration can significantly alter the vitreal kinetics of systemically administered drugs.
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