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Claudio Bucolo, Barbara Melilli, Cateno Piazza, Monia Zurria, Fabrizio Giulio, Filippo Drago; Indomethacin Eyedrops: Effect of Different Formulations on Ocular Pharmacokinetics in Rabbit. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4317.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the ocular pharmacokinetics of indomethacin following topical administration of two different formulations present in the market.
Rabbits received a single topical instillation (30 µl) of indomethacin ophthalmic suspension (IND-S; IndomTM Alfa-Intes) or indomethacin ophthalmic solution with hydroxypropyl-β-cyclodextrin (IND-CD; IndocollirioTM Bausch & Lomb), and aqueous humor, vitreous and retina were collected from animals at fixed time intervals after dosing. Indomethacin ocular levels were measured by LC/MS/MS, and PK parameters (Cmax, Tmax, and AUC0-240) were determined. All the animals were treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Peak concentrations of indomethacin in aqueous and vitreous were achieved within 30 min and 60 min after a single instillation of IND-S and IND-CD respectively. Retinal Tmax was 30 min and 120 min in IND-S-treated group and IND-CD-treated group respectively. Higher levels of indomethacin were found in retina after IND-S administration compared to IND-CD (AUC0-240 272.9 ng/g/min vs. AUC0-240 73.5 ng/g/min respectively; p<0.01). Also in the aqueous and vitreous the drug levels were statistically higher (p<0.01) in the IND-S group in comparison with the IND-CD group (AUC0-240 2039 ng/ml/min vs. AUC0-240 427.3 ng/ml/min, AUC0-240 53.8 ng/ml/min vs. AUC0-240 12.5 ng/ml/min respectively). Highest drug levels in the ocular tissues were found following IND-S administration compared with IND-CD (retina: Cmax 73.7 ± 6.4 ng/g vs. 25.5 ± 1.73 ng/g; aqueous: Cmax 952 ± 6.8 ng/ml vs. 163 ± 4.1 ng/ml; vitreous Cmax 31 ± 3.5 ng/ml vs. 6.37 ± 3.6 ng/ml).
IND-S treatment demonstrates a nonclinical ocular PK profile of indomethacin characterized by higher concentrations of drug in ocular tissues (4.7-, 4.3- and 3.7-fold higher in aqueous, vitreous and retina, respectively) compared to IND-CD-treated group. Taken together these data seem to indicate that IND-S formulation has good ocular distribution reaching relevant retinal indomethacin levels, and suggesting that this formulation may be useful in clinical practice for macular edema treatment.
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