Browsing by Subject "BETA-BLOCKING-AGENTS"

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  • Ramsay, Eva; del Amo, Eva M.; Toropainen, Elisa; Tengvall-Unadike, Unni; Ranta, Veli-Pekka; Urtti, Arto; Ruponen, Marika (2018)
    On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09-4.70x10(-6) cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be <5% and trans-conjunctival systemic absorption was 34-79% of the dose. Loss of drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability.
  • Fayyaz, Anam; Ranta, Veli-Pekka; Toropainen, Elisa; Vellonen, Kati-Sisko; Valtari, Annika; Puranen, Jooseppi; Ruponen, Marika; Gardner, Iain; Urtti, Arto; Jamei, Masoud; del Amo, Eva M. (2020)
    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.