Evaluation of the functional importance of organic cation transporters on the ocular disposition of its intravitreally injected substrate in rabbits.
OBJECTIVE
To evaluate the functional role of organic cation transporters (OCT) and ocular tissue distribution of intravitreally injected OCT substrate tetraethylammonium (TEA) in presence of OCT blocker (quinidine).


METHODS
New Zealand albino rabbits of either sex were used. Intravitreal quinidine pretreatment was made 30 min before the administration of TEA. Modulation of vitreous and ocular tissue kinetics of OCT substrate was evaluated with or without blocker pretreatment. Gamma scintigraphy was also performed to visualize the vitreous residence of (99m)Tc-labelled TEA in the presence and absence of blocker.


RESULTS
Intravitreally injected quinidine did not significantly alter the ocular disposition of TEA. TEA showed less significant posterior elimination kinetics and slow anterior elimination which resulted in longer residence time of TEA in eye after intravitreal administration.


CONCLUSIONS
Intravitreally injected OCT substrates may follow an anterior elimination pathway and prolonged residence time in vitreous humor. The present study shows that OCT may not be active from vitreous-to-blood route in the blood-retinal barrier.
Department of Ocular Pharmacology and Pharmacy, Dr.Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Jayabalan
J
Nirmal
Thirumurthy
T
Velpandian
Sundararajan Baskar
SB
Singh
Nihar Ranjan
NR
Biswas
Rajvardhan
R
Azad
Vasantha
V
Thavaraj
Gaurav
G
Mittal
Aseem
A
Bhatnagar
Supriyo
S
Ghose
D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D058449:Intravitreal Injections; D008297:Male; D027701:Organic Cation Transport Proteins / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000493:pharmacokinetics*; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits; D053719:Tandem Mass Spectrometry; D013667:Technetium; D019789:Tetraethylammonium / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism*; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology
D027701:Organic Cation Transport Proteins; D026902:Potassium Channel Blockers; D061567:Voltage-Gated Sodium Channel Blockers; D019789:Tetraethylammonium; D013667:Technetium; D011802:Quinidine