Evidence map›Paper›PMID 36195336›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2022

Activity and Expression of Carboxylesterases and Arylacetamide Deacetylase in Human Ocular Tissues.

Anam Hammid, John K Fallon, Toni Lassila, Paula Vieiro, Anusha Balla, Francisco Gonzalez, Arto Urtti, Philip C Smith, Ari Tolonen, Paavo Honkakoski

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In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Topical mycophenolate for the treatment of uveitis-associated inflammation.Journal of ophthalmic inflammation and infection · 2026
    Article
  4. Article
  5. Characterization of hydrolase activity in ocular tissues of humans and preclinical species.Drug metabolism and disposition: the biological fate of chemicals · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 4 countries.

Anam HammidSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.) paavo.honkakoski@uef.fi anam.hammid@uef.fi.ORCID 0000-0003-1939-7047
John K FallonSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).ORCID 0000-0003-1848-0121
Toni LassilaSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).
Paula VieiroSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).ORCID 0000-0001-6286-3512
Anusha BallaSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).ORCID 0000-0001-5225-6866
Francisco GonzalezSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).ORCID 0000-0002-1461-5474
Arto UrttiSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).
Philip C SmithSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).ORCID 0000-0003-2102-1209
Ari TolonenSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.).
Paavo HonkakoskiSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland (A.H., A.B., A.U., P.H.); Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.F., P.C.S.); Admescope Ltd, Oulu, Finland (T.L., A.T.); Biobank at the University Hospital at Santiago de Compostela, Santiago de Compostela, Spain (P.V.); Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, Santiago de Compostela, Spain (F.G.); Service of Ophthalmology, University Hospital of Santiago de Compostela and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela (F.G.); and Faculty of Pharmacy, University of Helsinki, Helsinki, Finland (A.U.) paavo.honkakoski@uef.fi anam.hammid@uef.fi.ORCID 0000-0002-4332-3577
University of North Carolina at Chapel Hill · US

Funding

Shared UPLC-MS/MS for Absolute Quantitative ProteomicsS10RR024595 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SMITH, PHILIP C · 2008 to 2008
$381k
NCRR NIH HHS S10 RR024595
6 · The paper itself

Abstract

As a multitissue organ, the eye possesses unique anatomy and physiology, including differential expression of drug-metabolizing enzymes. Several hydrolytic enzymes that play a major role in drug metabolism and bioactivation of prodrugs have been detected in ocular tissues, but data on their quantitative expression is scarce. Also, many ophthalmic drugs are prone to hydrolysis. Metabolic characterization of individual ocular tissues is useful for the drug development process, and therefore, seven individual ocular tissues from human eyes were analyzed for the activity and expression of carboxylesterases (CESs) and arylacetamide deacetylase (AADAC). Generic and selective human esterase substrates 4-nitrophenyl acetate (most esterases), D-luciferin methyl ester (CES1), fluorescein diacetate and procaine (CES2), and phenacetin (AADAC) were applied to determine the enzymes' specific activities. Enzyme kinetics and inhibition studies were performed with isoform-selective inhibitors digitonin (CES1) and verapamil and diltiazem (CES2). Enzyme contents were determined using quantitative targeted proteomics, and CES2 expression was confirmed by western blotting. The expression and activity of human CES1 among ocular tissues varied by >10-fold, with the highest levels found in the retina and iris-ciliary body. In contrast, human CES2 expression appeared lower and more similar between tissues, whereas AADAC could not be detected. Inhibition studies showed that hydrolysis of fluorescein diacetate is also catalyzed by enzymes other than CES2. This study provides, for the first time, quantitative information on the tissue-dependent expression of human ocular esterases, which can be useful for the development of ocular drugs, prodrugs, and in pharmacokinetic modeling of the eye. SIGNIFICANCE STATEMENT: Novel and comprehensive data on the protein expression and activities of carboxylesterases from individual human eye tissues are generated. In combination with previous reports on preclinical species, this study will improve the understanding of interspecies differences in ocular drug metabolism and aid the development of ocular pharmacokinetics models.

Indexed as

Carboxylic Ester HydrolasesProdrugsCarboxylesteraseFluoresceinsHumansHydrolysisCarboxylesteraseCarboxylic Ester HydrolasesdiacetylfluoresceinFluoresceinsProdrugs

Identifiers

PMID36195336
PMCPMC12164690
OpenAlexW4301395529

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.