September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Comparing Ocular pharmacokinetics of etoposide and its nanoemulsion after subtenon administration in rabbits

Author Affiliations & Notes
  • Santosh Kumar Patnaik
    Ocular Pharmacology & Pharmacy, AIIMS, New Delhi, Delhi, India
  • Deepti Maithani
    School of Pharmaceutical Sciences, Shobit University, Meerut, UP, India
  • Bhavna Chawla
    Opthalmology, AIIMS, New Delhi, Delhi, India
  • Vasantha Thavaraj
    Division of R.H.N, I.C.M.R, New Delhi, Delhi, India
  • Nihar R Biswas
    Pharmacology, AIIMS, New Delhi, India
  • Thirumurthy Velpandian
    Ocular Pharmacology & Pharmacy, AIIMS, New Delhi, Delhi, India
  • Footnotes
    Commercial Relationships   Santosh Patnaik, None; Deepti Maithani, None; Bhavna Chawla, None; Vasantha Thavaraj, None; Nihar R Biswas, None; Thirumurthy Velpandian, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1104. doi:
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      Santosh Kumar Patnaik, Deepti Maithani, Bhavna Chawla, Vasantha Thavaraj, Nihar R Biswas, Thirumurthy Velpandian; Comparing Ocular pharmacokinetics of etoposide and its nanoemulsion after subtenon administration in rabbits

      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):1104.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Approved commercial etoposide formulation is alcohol based formulation for intravenous administration. A nanoemulsion formulation of etoposide (NanoEt) has been developed and evaluated for its suitability for sub-tenon administration and compared with commercial formulation for its utilization in retinoblastoma.

Methods : NanoEt was freshly prepared under sterile condition using a validated method. New Zealand albino rabbits of either sex weighing 1.5 to 2.0 kg were divided into two groups. Test group received freshly prepared sterile 1mL of NanoEt (1mg/mL) and control group received 1mL alcohol based formulation of etoposide (1mg/mL) via subtenon under local anaesthesia to the left eye. Rabbits (n=4) for each time point were euthanized at 2hr, 6hr, 12hr, 24hr and 48hr following sub-tenon administration. Ocular tissues, humors and plasma samples were collected and quantified using LC-MS/MS. Unpaired Student’s t-test was used for statistical analysis.

Results : Etoposide levels in retina at 2 hr after subtenon administration for the test group was 4.7±1.3 µg/gm (Mean±SEM) and found to be 19.6 fold higher in a statistically significant manner (p=0.0253) as compared to control group showing 0.24±0.16 µg/gm. Comparing the systemic etoposide exposure as plasma AUC0-24 between both the groups, no significant difference was found. Etoposide levels reached in the contralateral eye of both the groups was also subjected to analysis and no significant difference was found. Interestingly this study has also observed that the retinal drug levels of etoposide for the test group was maintained more than the required IC50 value up to 23 hr of subtenon administration.

Conclusions : Etoposide nanoemulsion has got better bioavailability as compared to the commercial alcohol based formulation for subtenon injection. Low systemic exposure showed further advantage for its projected use in retinoblastoma. Further studies are required to evaluate its safety for its clinical utility.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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