RESUMO
A novel topical ophthalmic formulation of the preferential COX-2 inhibitor meloxicam has recently been developed. The purpose of the present study was to evaluate the efficacy and safety of this novel 0.03% meloxicam solution with regard to a reference 0.1% diclofenac formulation in a prospective, parallel, randomized, multicenter, double-blind study. Two groups of patients submitted to phacoemulsification with intraocular lens implantation were formed. Patients in one group were treated with meloxicam and those in the other group with diclofenac. Dosing was 1 drop t.i.d. for 30 days, beginning the first day after surgery, for both treatments. Inflammation was assessed by the presence of cells in the anterior chamber, anterior chamber flare, ciliary flush, photophobia and pain. Both treatments significantly reduced these indicators. Topical meloxicam and diclofenac produced a similar degree of burning sensation and conjunctival hyperemia. There was no significant difference between treatments in any of the measured parameters. It is concluded that the novel meloxicam solution is effective and safe. Meloxicam, however, did not offer any significant benefit over the diclofenac formulation in patients submitted to cataract surgery.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/administração & dosagem , Inflamação/prevenção & controle , Tiazinas/administração & dosagem , Tiazóis/administração & dosagem , Administração Tópica , Idoso , Câmara Anterior/metabolismo , Câmara Anterior/patologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Inflamação/etiologia , Implante de Lente Intraocular/efeitos adversos , Masculino , Meloxicam , Pessoa de Meia-Idade , Soluções Oftálmicas , Facoemulsificação/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Tiazinas/efeitos adversos , Tiazóis/efeitos adversosRESUMO
AIM: To determine the efficacy of meloxicam ophthalmic formulation on COX-2 activity and expression, inflammation-related cytokines expression and inflammation in an ocular inflammation model. METHODS: Ocular inflammation was induced in New Zealand rabbits by topical application of croton oil (3%) for 3 h. An ophthalmic solution of 0.03% meloxicam, 0.1% sodium diclofenac or vehicle (Sophisen) was administered every 4 h. Conjunctiva, cornea, aqueous humour and vitreous humour were collected. RESULTS: In irritated eyes, 72 h of meloxicam treatment downregulated COX-2 expression and activity (mRNA by RT-PCR and PGE2 levels by ELISA, respectively) in a time-dependent manner and reduced inflammation. Meanwhile, diclofenac failed to reduce COX-2 mRNA or PGE2 to basal levels after 7 days of treatment. Meloxicam treatment downregulated IL-6 and IFN-gamma expression in the conjunctiva and IL-1beta and TNF-alpha expression in the cornea. Diclofenac failed to modify these cytokines in both tissues. Meloxicam treatment increased the expression of IL-6 in conjunctiva, and IL-10 in cornea, while diclofenac had no effect on these cytokines. CONCLUSION: Meloxicam treatment was more efficient than diclofenac in downregulating the expression and activity of COX-2, reducing inflammation, and modifying the inflammatory-related cytokines.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Endoftalmite/metabolismo , Tiazinas/farmacologia , Tiazóis/farmacologia , Doença Aguda , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Humor Aquoso/metabolismo , Córnea/efeitos dos fármacos , Córnea/metabolismo , Córnea/patologia , Óleo de Cróton , Ciclo-Oxigenase 2/genética , Citocinas/genética , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Endoftalmite/induzido quimicamente , Endoftalmite/patologia , Masculino , Meloxicam , Soluções Oftálmicas , RNA Mensageiro/genética , CoelhosRESUMO
Sophisen, a new ophthalmic drug carrier, was characterized using physicochemical and morphological criteria. Diclofenac belongs to a nonsteroidal anti-inflammatory molecule group and its ophthalmic use avoids side effects produced by steroid drugs. Cyclosporine-A is a cyclic peptide used as an immunosuppressive when administrated systemically. Its application in ophthalmology has been reported, but it is a very poor soluble drug. Diclofenac sodium and Cyclosporine-A were mixed with Sophisen to render two new ophthalmic solutions that were named 3A Ofteno and Modusik-A Ofteno, respectively. Based on transmission electron microscopy and dynamic light scattering studies, we concluded that Sophisen is a polydisperse solution with a molecular weight of 413 +/-122 kDa, whereas 3A Ofteno and Modusik-A Ofteno are monodisperse solutions with molecular weights of 169 +/- 44 and 153 +/- 10, respectively. Sophisen was shown to be a good carrier for diclofenac sodium as evaluated by passive diffusion through the cornea. A comparative study suggests that diclofenac applied as eye drops was better tolerated when associated with Sophisen. In addition, Modusik-A Ofteno, a new aqueous solution of Cyclosporine-A, improved tear production in patients with moderate or severe dry eye condition.