Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability

Vincent H.‐L Lee, Kim W. Morimoto, Robert Stratford Jr.

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers— epithelium and stroma‐endothelium—so as to anticipate the extent to which drugs containing ester linkages will be metabolized during transport. This has been achieved by incubating corneal homogenates of albino and pigmented rabbits of various age groups with α‐naphthyl acetate, the model substrate, and monitoring the fluorescence intensity due to α‐naphthol as a function of time. The results indicate that: (1) esterase activity in the epithelium is approximately twice that in the stroma‐endothelium; (2) esterase activity in the intact cornea is linearly related to those in the epithelium and the stroma‐endothelium; and (3) the esterase activity in the cornea and its component layers varies with rabbit's age and strain. According to these results the bulk of esterase‐mediated hydrolysis is expected to take place in the epithelium, so that the residence time of a drug in this tissue can have a significant impact on its ocular bioavailability.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalBiopharmaceutics & Drug Disposition
Volume3
Issue number4
DOIs
StatePublished - Jan 1 1982
Externally publishedYes

Fingerprint

Esterases
Cornea
Biological Availability
Rabbits
Epithelium
Pharmaceutical Preparations
Naphthols
Carboxylesterase
Drug Resistance
Esters
Hydrolysis
Age Groups
Fluorescence
Research

Keywords

  • Age variation
  • Corneal esterases
  • Ocular drug bioavailability
  • Ocular drug metabolism
  • Pigmentation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability. / Lee, Vincent H.‐L; Morimoto, Kim W.; Stratford Jr., Robert.

In: Biopharmaceutics & Drug Disposition, Vol. 3, No. 4, 01.01.1982, p. 291-300.

Research output: Contribution to journalArticle

@article{cbcf9dea67d74d239a1b3435b4c45b69,
title = "Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability",
abstract = "Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers— epithelium and stroma‐endothelium—so as to anticipate the extent to which drugs containing ester linkages will be metabolized during transport. This has been achieved by incubating corneal homogenates of albino and pigmented rabbits of various age groups with α‐naphthyl acetate, the model substrate, and monitoring the fluorescence intensity due to α‐naphthol as a function of time. The results indicate that: (1) esterase activity in the epithelium is approximately twice that in the stroma‐endothelium; (2) esterase activity in the intact cornea is linearly related to those in the epithelium and the stroma‐endothelium; and (3) the esterase activity in the cornea and its component layers varies with rabbit's age and strain. According to these results the bulk of esterase‐mediated hydrolysis is expected to take place in the epithelium, so that the residence time of a drug in this tissue can have a significant impact on its ocular bioavailability.",
keywords = "Age variation, Corneal esterases, Ocular drug bioavailability, Ocular drug metabolism, Pigmentation",
author = "Lee, {Vincent H.‐L} and Morimoto, {Kim W.} and {Stratford Jr.}, Robert",
year = "1982",
month = "1",
day = "1",
doi = "10.1002/bdd.2510030402",
language = "English (US)",
volume = "3",
pages = "291--300",
journal = "Biopharmaceutics and Drug Disposition",
issn = "0142-2782",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability

AU - Lee, Vincent H.‐L

AU - Morimoto, Kim W.

AU - Stratford Jr., Robert

PY - 1982/1/1

Y1 - 1982/1/1

N2 - Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers— epithelium and stroma‐endothelium—so as to anticipate the extent to which drugs containing ester linkages will be metabolized during transport. This has been achieved by incubating corneal homogenates of albino and pigmented rabbits of various age groups with α‐naphthyl acetate, the model substrate, and monitoring the fluorescence intensity due to α‐naphthol as a function of time. The results indicate that: (1) esterase activity in the epithelium is approximately twice that in the stroma‐endothelium; (2) esterase activity in the intact cornea is linearly related to those in the epithelium and the stroma‐endothelium; and (3) the esterase activity in the cornea and its component layers varies with rabbit's age and strain. According to these results the bulk of esterase‐mediated hydrolysis is expected to take place in the epithelium, so that the residence time of a drug in this tissue can have a significant impact on its ocular bioavailability.

AB - Being the major pathway by which topically applied ophthalmic drugs enter the eye, the cornea can control the amount of active drug ultimately absorbed by offering resistance to drug permeation and by metabolizing the drug during permeation. This research seeks to determine the esterase activity in the cornea and two of its component layers— epithelium and stroma‐endothelium—so as to anticipate the extent to which drugs containing ester linkages will be metabolized during transport. This has been achieved by incubating corneal homogenates of albino and pigmented rabbits of various age groups with α‐naphthyl acetate, the model substrate, and monitoring the fluorescence intensity due to α‐naphthol as a function of time. The results indicate that: (1) esterase activity in the epithelium is approximately twice that in the stroma‐endothelium; (2) esterase activity in the intact cornea is linearly related to those in the epithelium and the stroma‐endothelium; and (3) the esterase activity in the cornea and its component layers varies with rabbit's age and strain. According to these results the bulk of esterase‐mediated hydrolysis is expected to take place in the epithelium, so that the residence time of a drug in this tissue can have a significant impact on its ocular bioavailability.

KW - Age variation

KW - Corneal esterases

KW - Ocular drug bioavailability

KW - Ocular drug metabolism

KW - Pigmentation

UR - http://www.scopus.com/inward/record.url?scp=0020413888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020413888&partnerID=8YFLogxK

U2 - 10.1002/bdd.2510030402

DO - 10.1002/bdd.2510030402

M3 - Article

VL - 3

SP - 291

EP - 300

JO - Biopharmaceutics and Drug Disposition

JF - Biopharmaceutics and Drug Disposition

SN - 0142-2782

IS - 4

ER -