title: Role of organic cation transporters in the ocular disposition of its intravenously injected substrate in rabbits: implications for ocular drug therapy.
abstract: The present study was conducted to test the hypothesis; OCT may be active from blood-to-vitreous for the uptake of its substrates. Ocular uptake of Tetraethylammonium (TEA) across blood ocular barriers and the tissue distribution was evaluated in vivo in New Zealand albino rabbits after intravenous administration. Quinidine (blocker) pretreatment resulted in a significant (p < 0.05) reduction in the Area Under the Curve (AUC) of TEA in vitreous (4.2 fold) and aqueous humor (1.8 fold) as compared to the control group which supports the role of OCT in uptake transport of its substrate across Blood ocular barrier. The blockade of OCT also affected the elimination of its substrate resulting in increased plasma levels. In most of the tissues, OCT are functionally present from apical to basolateral. The gene expression studies also showed the presence of OCT1, OCTN1 and OCTN2 in various ocular tissues studied. The present findings suggest that OCT are functionally active in blood ocular barriers and involved in the transport of its substrate from blood-to-vitreous humor.
authors.affiliation: 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.
authors.forename: Jayabalan
authors.initials: J
authors.lastname: Nirmal
authors.forename: Anju
authors.initials: A
authors.lastname: Sirohiwal
authors.forename: Sundararajan Baskar
authors.initials: SB
authors.lastname: Singh
authors.forename: Nihar Ranjan
authors.initials: NR
authors.lastname: Biswas
authors.forename: Vasantha
authors.initials: V
authors.lastname: Thavaraj
authors.forename: Raj Vardhan
authors.initials: RV
authors.lastname: Azad
authors.forename: Thirumurthy
authors.initials: T
authors.lastname: Velpandian
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001692:Biological Transport; D001813:Blood-Retinal Barrier / Q000502:physiology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation; D007275:Injections, Intravenous; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics; D012313:RNA / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019789:Tetraethylammonium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D026902:Potassium Channel Blockers; D012313:RNA; D019789:Tetraethylammonium
keywords: blood-to-vitreous transport; intravenous; ocular; organic cation transporters; pharmacokinetics; rabbits