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C. Tsika, A. Tsourdou, M. Tzatzarakis, S. K. Charissis, V. F. Diakonis, S. Plainis, M. K. Tsilimbaris; Assessment of the Intravitreal Pharmacokinetics and Potential Retinal Toxicity of the NSAID Lornoxicam. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4746.
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To evaluate the pharmacokinetic and toxicological profile of intravitreally injected lornoxicam in rabbit eyes.
For the determination of the pharmacokinetic characteristics of the drug, both eyes of 15 albino rabbits were intravitreally (IVT) injected with 250 µg of commercially available lornoxicam (Xefo® 8 IV/IM Injection, Nycomed Hellas S.A.). Both eyes of 3 rabbits were enucleated at time points 0(right after injection), 1, 2, 6 and 24 hours after injection. Lornoxicam was extracted (LLE) from the vitreous and sample concentrations were measured with HPLC (UV/VIS). For the investigation of retinal toxicity of intravitreal lornoxicam, two concentrations of the drug were tested in 10 albino rabbits that formed two groups of 5 animals. Group I (low dose-group) received intravitreally 250 µg/0.1 ml of lornoxicam and Group II (high dose-group) 1.500µg/0.1 ml of lornoxicam, always in the right eyes (study eyes), while the fellow eyes served as controls (received 0.1ml of Water For Injection intravitreally). All animals underwent indirect ophthalmoscopy, tonometry and electroretinography before the injection (day 0), at day 1, 15 and 30 after the injection. At the end of follow-up, all animals were sacrificed and the retinas were isolated and prepared for histological examination. For the statistical analysis of the data, Repeated measures ANOVA (SPSS v 17.0)was used.
Lornoxicam was detected at 372nm. It was found to follow first order kinetics, with an elimination rate constant of 0.235h-1 and a half-life of 3.0 hrs. No difference was observed in indirect ophthalmoscopy findings before and in any time point after injection. For the ensemble of values, no significant difference in IOP was detected at any time point tested (p=0.419). Moreover, the amplitude of either photopic or scotopic flash b-waves in ERG didn’t prove to differ significantly with time (p= 0.154 and p = 0.568 respectively). Eventually, in Group I the study eye retinas didn’t differ histologically from the controls, whereas in Group II extended retinal damage was observed in the study eyes.
Intravitreal lornoxicam causes dose-related toxic effect to the retina. On the other hand, a dose smaller or equal to 250 µg is safe and could be considered as an alternative treatment to ocular inflammatory conditions.
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