Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry

Deepta A Ghate, William Brooks, Bernard E. McCarey, Henry F. Edelhauser

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

PURPOSE. To evaluate the pharmacokinetics of the periocular injections: posterior subtenon (PST), retrobulbar (RB), and subconjunctival (SC) injection. METHODS. Two sodium fluorescein (NaF) concentrations, 2.5 mg in 0.1 mL (NaF1) and 2.5 mg in 0.5 mL (NaF2) were injected into live rabbits by the PST (NaF1 n = 4, NaF2 n = 3), RB (NaF1 n = 10), SC (NaF1 n = 6), and intravenous (IV, NaF1 n = 6) routes and into euthanatized rabbits by the RB (NaF1 n = 8) route. NaF concentrations in the choroid/retina, vitreous, and anterior segment were measured by ocular fluorophotometry. The NaF level in the contralateral choroid/retina was used as a measure of the systemic drug levels. RESULTS. The maximum NaF concentrations (nanograms per milliliter) in the choroid/retina after PST, RB, SC, and IV were 757 ± 549 at 2 hours, 906 ± 1014 at 1 hour, 320 ± 462 at 2 hours, and 865 ± 363 at 5 to 10 minutes, respectively. The PST had the highest and most prolonged vitreous NaF1 concentration (maximum: 270 ± 226 ng/mL at 3-5 hours). The contralateral peak choroid/retina NaF levels after the RB, SC, and FV injections were 7, 4, and 21 times greater than after the PST injection. The SC injection had the highest anterior segment NaF concentration (5364 ± 2840 ng/mL at 2 hours). PST with NaF2 resulted in intraocular NaF levels higher than with NaF1. CONCLUSIONS. NaF reaches the choroid/retina by transscleral diffusion from the periocular depot. The orbital and conjunctival vasculature and lymphatics have a larger role in NaF clearance than does the choroid. NaF diffuses into the vitreous from the choroid and the anterior segment; the periocular depot location determines the predominant diffusion pathway. The duration of high NaF levels in the choroid/retina or the anterior segment determines vitreous NaF levels. PST is the best periocular route for vitreous NaF delivery with minimal systemic levels. Increasing the volume of NaF PST depot enhances transscleral drug delivery.

Original languageEnglish (US)
Pages (from-to)2230-2237
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number5
DOIs
StatePublished - May 1 2007

Fingerprint

Fluorophotometry
Intraocular Injections
Choroid
Pharmacokinetics
Retina
Pharmaceutical Preparations
Injections
Rabbits
Fluorescein

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry. / Ghate, Deepta A; Brooks, William; McCarey, Bernard E.; Edelhauser, Henry F.

In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 5, 01.05.2007, p. 2230-2237.

Research output: Contribution to journalArticle

Ghate, Deepta A ; Brooks, William ; McCarey, Bernard E. ; Edelhauser, Henry F. / Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry. In: Investigative Ophthalmology and Visual Science. 2007 ; Vol. 48, No. 5. pp. 2230-2237.
@article{227bb94f49d346cd8342314e90464046,
title = "Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry",
abstract = "PURPOSE. To evaluate the pharmacokinetics of the periocular injections: posterior subtenon (PST), retrobulbar (RB), and subconjunctival (SC) injection. METHODS. Two sodium fluorescein (NaF) concentrations, 2.5 mg in 0.1 mL (NaF1) and 2.5 mg in 0.5 mL (NaF2) were injected into live rabbits by the PST (NaF1 n = 4, NaF2 n = 3), RB (NaF1 n = 10), SC (NaF1 n = 6), and intravenous (IV, NaF1 n = 6) routes and into euthanatized rabbits by the RB (NaF1 n = 8) route. NaF concentrations in the choroid/retina, vitreous, and anterior segment were measured by ocular fluorophotometry. The NaF level in the contralateral choroid/retina was used as a measure of the systemic drug levels. RESULTS. The maximum NaF concentrations (nanograms per milliliter) in the choroid/retina after PST, RB, SC, and IV were 757 ± 549 at 2 hours, 906 ± 1014 at 1 hour, 320 ± 462 at 2 hours, and 865 ± 363 at 5 to 10 minutes, respectively. The PST had the highest and most prolonged vitreous NaF1 concentration (maximum: 270 ± 226 ng/mL at 3-5 hours). The contralateral peak choroid/retina NaF levels after the RB, SC, and FV injections were 7, 4, and 21 times greater than after the PST injection. The SC injection had the highest anterior segment NaF concentration (5364 ± 2840 ng/mL at 2 hours). PST with NaF2 resulted in intraocular NaF levels higher than with NaF1. CONCLUSIONS. NaF reaches the choroid/retina by transscleral diffusion from the periocular depot. The orbital and conjunctival vasculature and lymphatics have a larger role in NaF clearance than does the choroid. NaF diffuses into the vitreous from the choroid and the anterior segment; the periocular depot location determines the predominant diffusion pathway. The duration of high NaF levels in the choroid/retina or the anterior segment determines vitreous NaF levels. PST is the best periocular route for vitreous NaF delivery with minimal systemic levels. Increasing the volume of NaF PST depot enhances transscleral drug delivery.",
author = "Ghate, {Deepta A} and William Brooks and McCarey, {Bernard E.} and Edelhauser, {Henry F.}",
year = "2007",
month = "5",
day = "1",
doi = "10.1167/iovs.06-0954",
language = "English (US)",
volume = "48",
pages = "2230--2237",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "5",

}

TY - JOUR

T1 - Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry

AU - Ghate, Deepta A

AU - Brooks, William

AU - McCarey, Bernard E.

AU - Edelhauser, Henry F.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - PURPOSE. To evaluate the pharmacokinetics of the periocular injections: posterior subtenon (PST), retrobulbar (RB), and subconjunctival (SC) injection. METHODS. Two sodium fluorescein (NaF) concentrations, 2.5 mg in 0.1 mL (NaF1) and 2.5 mg in 0.5 mL (NaF2) were injected into live rabbits by the PST (NaF1 n = 4, NaF2 n = 3), RB (NaF1 n = 10), SC (NaF1 n = 6), and intravenous (IV, NaF1 n = 6) routes and into euthanatized rabbits by the RB (NaF1 n = 8) route. NaF concentrations in the choroid/retina, vitreous, and anterior segment were measured by ocular fluorophotometry. The NaF level in the contralateral choroid/retina was used as a measure of the systemic drug levels. RESULTS. The maximum NaF concentrations (nanograms per milliliter) in the choroid/retina after PST, RB, SC, and IV were 757 ± 549 at 2 hours, 906 ± 1014 at 1 hour, 320 ± 462 at 2 hours, and 865 ± 363 at 5 to 10 minutes, respectively. The PST had the highest and most prolonged vitreous NaF1 concentration (maximum: 270 ± 226 ng/mL at 3-5 hours). The contralateral peak choroid/retina NaF levels after the RB, SC, and FV injections were 7, 4, and 21 times greater than after the PST injection. The SC injection had the highest anterior segment NaF concentration (5364 ± 2840 ng/mL at 2 hours). PST with NaF2 resulted in intraocular NaF levels higher than with NaF1. CONCLUSIONS. NaF reaches the choroid/retina by transscleral diffusion from the periocular depot. The orbital and conjunctival vasculature and lymphatics have a larger role in NaF clearance than does the choroid. NaF diffuses into the vitreous from the choroid and the anterior segment; the periocular depot location determines the predominant diffusion pathway. The duration of high NaF levels in the choroid/retina or the anterior segment determines vitreous NaF levels. PST is the best periocular route for vitreous NaF delivery with minimal systemic levels. Increasing the volume of NaF PST depot enhances transscleral drug delivery.

AB - PURPOSE. To evaluate the pharmacokinetics of the periocular injections: posterior subtenon (PST), retrobulbar (RB), and subconjunctival (SC) injection. METHODS. Two sodium fluorescein (NaF) concentrations, 2.5 mg in 0.1 mL (NaF1) and 2.5 mg in 0.5 mL (NaF2) were injected into live rabbits by the PST (NaF1 n = 4, NaF2 n = 3), RB (NaF1 n = 10), SC (NaF1 n = 6), and intravenous (IV, NaF1 n = 6) routes and into euthanatized rabbits by the RB (NaF1 n = 8) route. NaF concentrations in the choroid/retina, vitreous, and anterior segment were measured by ocular fluorophotometry. The NaF level in the contralateral choroid/retina was used as a measure of the systemic drug levels. RESULTS. The maximum NaF concentrations (nanograms per milliliter) in the choroid/retina after PST, RB, SC, and IV were 757 ± 549 at 2 hours, 906 ± 1014 at 1 hour, 320 ± 462 at 2 hours, and 865 ± 363 at 5 to 10 minutes, respectively. The PST had the highest and most prolonged vitreous NaF1 concentration (maximum: 270 ± 226 ng/mL at 3-5 hours). The contralateral peak choroid/retina NaF levels after the RB, SC, and FV injections were 7, 4, and 21 times greater than after the PST injection. The SC injection had the highest anterior segment NaF concentration (5364 ± 2840 ng/mL at 2 hours). PST with NaF2 resulted in intraocular NaF levels higher than with NaF1. CONCLUSIONS. NaF reaches the choroid/retina by transscleral diffusion from the periocular depot. The orbital and conjunctival vasculature and lymphatics have a larger role in NaF clearance than does the choroid. NaF diffuses into the vitreous from the choroid and the anterior segment; the periocular depot location determines the predominant diffusion pathway. The duration of high NaF levels in the choroid/retina or the anterior segment determines vitreous NaF levels. PST is the best periocular route for vitreous NaF delivery with minimal systemic levels. Increasing the volume of NaF PST depot enhances transscleral drug delivery.

UR - http://www.scopus.com/inward/record.url?scp=34250163534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250163534&partnerID=8YFLogxK

U2 - 10.1167/iovs.06-0954

DO - 10.1167/iovs.06-0954

M3 - Article

VL - 48

SP - 2230

EP - 2237

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 5

ER -