Comprehensive ocular and systemic pharmacokinetics of dexamethasone after subconjunctival and intravenous injections in rabbits.

Autor: Valtari A; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Posio S; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Toropainen E; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Balla A; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Puranen J; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Sadeghi A; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Ruponen M; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Ranta VP; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Vellonen KS; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland., Urtti A; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland; University of Helsinki, Faculty of Pharmacy, Drug Research Program, Yliopistonkatu 3, 00014 Helsinki, Finland., Amo EMD; University of Eastern Finland, School of Pharmacy, Biopharmaceutics, Yliopistonranta 1, 70210 Kuopio, Finland. Electronic address: eva.delamo@uef.fi.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 May; Vol. 198, pp. 114260. Date of Electronic Publication: 2024 Mar 12.
DOI: 10.1016/j.ejpb.2024.114260
Abstrakt: Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics. Dexamethasone concentrations in plasma (after subconjunctival and intravenous injections) and four ocular tissues (iris-ciliary body, aqueous humour, neural retina and vitreous) were analysed using LC-MS/MS. Population pharmacokinetic modelling for plasma data from both injection routes were used, and for first time the constant rate of absorption of dexamethasone from the subconjunctival space into plasma was estimated (k a,plasma  = 0.043 min -1 , i.e. absorption half-life of 17.3 min). Non-compartmental analysis was used for the ocular data analysis and resulting in ocular drug exposure of iris-ciliary body (AUC 0-∞ = 41984 min·ng/g) > neural retina (AUC 0-∞ = 25511 min·ng/g) > vitreous (AUC 0-∞ = 7319 min·ng/mL) > aqueous humour (AUC 0-∞ = 6146 min·ng/mL). The absolute bioavailability values after subconjunctival injection, reported for the first time, were 0.74 % in aqueous humour (comparable to topical dexamethasone suspensions), and 0.30 % in vitreous humour (estimated to be higher than in topical administration). These novel and comprehensive pharmacokinetic data provide valuable information on the potential for exploiting this route in ocular drug development for treating both, anterior and posterior segment ocular diseases. Moreover, the new generated dexamethasone-parameters are a step-forward in building predictive pharmacokinetic models to support the design of new subconjunctival dexamethasone formulations, which may sustain drug effect for longer period of time.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: