Influence of Dosage Form on the Intravitreal Pharmacokinetics of Diclofenac

摘要: Anti-inflammatory corticosteroids are being used in the clinical settings for treatment of age-related macular degeneration (AMD) and diabetic edema, which common causes vision loss United States.1–4 However, due to high prevalence side effects associated with use corticosteroids,4,5 there is a need identify other anti-inflammatory agents better safety profile. Recent studies have demonstrated usefulness nonsteroidal drugs (NSAIDs) as an alternative.6–8 NSAIDs potent cyclooxygenase (COX) inhibitors agents, potential antiproliferative antiangiogenic well.9 Also, not cataract formation or elevated intraocular pressure,10 main intravitreal corticosteroids. Since topical administration does deliver appreciable drug quantities posterior segment,11 remains viable option treating segment disease. repeated injections entail risk retinal detachment endophthalmitis. A possible alternative frequent solutions development sustained release systems molecules prolonged half-lives reduce injection-related complications, provide enhanced duration effects, any high-peak-concentration–related encountered solution form drug. Diclofenac, NSAID, exerts its action by inhibition both COX lipoxygenase pathways.12 Although diclofenac has been topically inflammatory conditions, recent focus on delivery (Baranano DE et al. IOVS 2008;49:ARVO E-Abstract 5606).13 Diclofenac sodium was found be safe nontoxic up dose 0.3 mg after administration. low-molecular-weight (MWt: 318.13), when solution, case commercial ophthalmic formulations, it predicted disappear rapidly from vitreous humor, short half life 2.87 hours.14 To maintain levels periods eye, slow-release such nanoparticles,15,16 microparticles,9 implants17 may useful. Alternatively, suspension less soluble useful prolonging delivery. For instance, triamcinolone acetonide known sustain 8 months.18 Keeping earlier success mind, objective this study prepare assess dosage acid compare solution. pigmented rabbit model study, because human eyes pigmented19 elimination vitreous14 back eye can influenced pigmentation.20 Furthermore, pharmacokinetic models were developed explain tissues forms.