May 2003
Volume 44, Issue 13
ARVO Annual Meeting Abstract  |   May 2003
Ocular Disposition of a P-Glycoprotein Substrate, Quinidine
Author Affiliations & Notes
  • S. Duvvuri
    Pharmaceutical Sciences, University of Missouri-kansas City, Kansas City, MO, United States
  • A.K. Mitra
    Pharmaceutical Sciences, University of Missouri-kansas City, Kansas City, MO, United States
  • Footnotes
    Commercial Relationships  S. Duvvuri, None; A.K. Mitra, None.
  • Footnotes
    Support  R01 EY09171, R01 EY10659
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 4446. doi:
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      S. Duvvuri, A.K. Mitra; Ocular Disposition of a P-Glycoprotein Substrate, Quinidine . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4446.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose: Blood-retinal barrier (BRB) constraints the passage of substances from blood into the retina and vitreous humor. BRB is expressed at two levels, i) endothelial cells of blood vessels supplying blood to neural retina (iBRB) and ii) retinal pigmented epithelium (RPE). P-glycoprotein (P-gp) has been shown to be expressed on various blood-tissue barriers. The aim of the project is to study the expression and role of P-gp on BRB and its effect on permeation of quinidine, a P-gp substrate, from blood into the ocular fluids. Methods: Male New Zealand albino rabbits (2-2.5 kg) were employed for the studies. Microdialysis technique was employed to sample the vitreous and aqueous humors upon systemic (5 mg/kg) and intravitreal (15 nmoles and 1.5 nmoles) administration of quinidine. Kinetics of quinidine were studied in the presence and absence of verapamil, to study the effect of P-gp inhibitors on ocular kinetics of quinidine over a period of 10 hr. Western-blot analysis of retina-choroid for presence of P-gp was done on retina-choroid for identifying the presence of P-gp on the tissue. Results: Quinidine was found to have an elimination half-life of 163.133±65.93 min and165.083±31.509 min and AUC of 16.052±7.208 min*µgm/ml and 19.216±3.736 min*µgm/ml in aqueous and vitreous humors, respectively. In the presence of verapamil (0.2µmoles) in the eye, the AUC of quinidine in aqueous and vitreous humors increased significantly (p<0.05), the values being 52.404±12.06min*µgm/ml and 39.278±6.477min*µgm/ml, respectively. Vitreal kinetic studies with quinidine (1.5 nmoles) reveal faster elimination of quinidine from the vitreous in the presence of verapamil (0.0046±0.0005 min-1) when compared to the control (0.0072±0.0003 min-1). Western-blot analysis revealed the presence of P-gp on retina-choroid. Conclusions: P-gp could be a limiting factor in low permeation of quinidine from blood to vitreous and aqueous humors. Inhibition studies with verapamil indicate the presence of P-gp on BRB and its efflux action on systemically administered quinidine. Results from Western-blot analysis suggest that P-gp could be expressed on the BRB. Moreover, vitreal kinetic studies with quinidine indicate towards the expression of P-gp on the retina facing the vitreous, inhibiting entry of compounds into the retina from vitreous.

Keywords: retina • animal model • anterior segment 

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