| Abstract |
INTRODUCTION. Lornoxicam is a water-soluble, non-steroid anti-inflammatory drug (NSAID) of the oxicam class, which is delivered systemically for the management of pain. The anti-inflamatory properties of this drug category are attributed to the inhibition of prostaglandin synthesis, which are mediated to inflammatory responses and anaphylaxis. Until today, corticosteroids have been a standard treatment for various inflammatory ocular conditions, such as cystoid macular edema, diabetic macular edema, uveitis and age-related macular degeneration. But unfortunately, reported side effects of intravitreal steroids include intraocular pressure elevation and cataract development. Consequently, this fact generates the need for the determination of an alternative treatment. Generally, it is desirable to find a drug with a prolonged half-life, thus a longer duration of therapeutic action, which will not cause deleterious effects to the retina. PURPOSE. Aim of this study is to evaluate the pharmacokinetic and toxicological profile of intravitreally injected lornoxicam ιn rabbits. METHODS. For the determination of the pharmacokinetic characteristics of the drug, both eyes of 15 albino rabbits were intravitreally injected with 250 μg of commercially available lornoxicam (for intravenous/intramuscular use, Xefo®
RESULTS. Lornoxicam is eliminated from the vitreous by a first order kinetic process with 8 IV/IM Injection, Nycomed Hellas S.A.). The eyes of 3 rabbits were enucleated at time points 0, 1, 2, 6 and 24 hours after the injection was performed. Lornoxicam concentrations were measured in the vitreous humor with an HPLC-UV/VIS detector. In another experiment, 10 albino rabbits were recruited to ascertain if an intravitreal injection of lornoxicam exhibited retinal toxicity. The animals were divided into two groups (I and II). Two different concentrations of lornoxicam wee prepared, 250 μg/ 0.1 ml and 1500 μg/ 0.1 ml. Group I received the low dose and group II received the high dose. The right eyes were injected with the drug solution (experimental eyes), whereas the left eyes were injected with 0.1 ml water for injection (control eyes). All animals underwent clinical inspection by indirect ophthalmoscopy, tonometry and electroretinography (ERG) before the injection was performed. The same series of examinations were repeated at days 1, 15 and 30 after the injection was performed. At the end of the follow-up period, the animals were sacrificed and the retinas were examined by light microscopy.
an elimination rate constant of 0.235h-1 and a half-life of 3.0 h. Repeated mesures ANOVA demonstrated no significant effect between intraocular pressure and time [F(3,24) = 0,979, p = 0,419], or beween photopic flash b-wave and time [F(3,24) = 0,112, p = 0,952], or between
scotopic flash b-wave and time [F(3,24) = 1,918, p = 0,568]. On the contrary, histological examination of the samples revealed extended retinal damage of group II experimental eyes, whereas the morphology of the group I experimental eyes did not differ from that of the control eyes. CONCLUSIONS. 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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Μελέτη της κάθαρσης και της τοξικότητας της λορνοξικάμης μετά από ενδοϋαλοειδική χορήγηση σε αλφικά κουνέλια
