Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in rabbits.


Journal

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982

Informations de publication

Date de publication:
01 Dec 2020
Historique:
received: 24 06 2020
revised: 02 09 2020
accepted: 07 09 2020
pubmed: 19 9 2020
medline: 22 6 2021
entrez: 18 9 2020
Statut: ppublish

Résumé

Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the albino rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS. The pharmacokinetic parameters were estimated using compartmental and non-compartmental analyses. The ocular bioavailability was covering broad range of values: atenolol (0.07 %), timolol (1.22%, 1.51%) and betaxolol (3.82%, 4.31%). Absolute ocular bioavailability presented a positive trend with lipophilicity and the values showed approximately 60-fold range. The generated data enhances our understanding for ocular pharmacokinetics of drugs and may be utilized in pharmacokinetic model building in ophthalmic drug development.

Identifiants

pubmed: 32946960
pii: S0928-0987(20)30341-9
doi: 10.1016/j.ejps.2020.105553
pii:
doi:

Substances chimiques

Adrenergic beta-Antagonists 0
Ophthalmic Solutions 0
Atenolol 50VV3VW0TI
Timolol 817W3C6175
Betaxolol O0ZR1R6RZ2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

105553

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Anam Fayyaz (A)

Certara UK, Simcyp Division, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, United Kingdom; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Veli-Pekka Ranta (VP)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Elisa Toropainen (E)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Kati-Sisko Vellonen (KS)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Annika Valtari (A)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Jooseppi Puranen (J)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Marika Ruponen (M)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland.

Iain Gardner (I)

Certara UK, Simcyp Division, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, United Kingdom.

Arto Urtti (A)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland; University of Helsinki, Faculty of Pharmacy, Drug Research Program, Yliopistonkatu 3, Helsinki 00014, Finland; Saint-Petersburg State University, Institute of Chemistry, Universitetskiy Prospekt, 26, Petergoff 198504, Russian Federation.

Masoud Jamei (M)

Certara UK, Simcyp Division, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, United Kingdom.

Eva M Del Amo (EM)

University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, Kuopio 70210, Finland. Electronic address: eva.delamo@uef.fi.

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Classifications MeSH