Clinical Trial of an Aldose Reductase Inhibitor in Diabetic Neuropathy

Handelsman, D J; Turtle, John R.

doi:10.2337/diab.30.6.459

Cited by 66 publications

(21 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With tolrestat, the major side effect was hepatic damage with concomitant elevation of liver enzymes in 2% of the patients (Macleod et al 1992). With alrestatin, increased liver transaminases, severe liver reaction, leucopenia and photosensitive skin rashes were reported (Fagius & Jameson 1981;Handelsman & Turtle 1981). These side effects were attributed to non-specific inhibition of a similar oxidoreductase family of enzymes, such as aldehyde reductase and alcohol dehydrogenase, by these ARIs (Sato & Kador 1990;Pfeifer et al 1997;Oates & Mylari 1999).…”

Section: Introductionmentioning

confidence: 99%

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

Sunkara

Ayalasomayajula

Rao

et al. 2004

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

To better develop N- [4-(benzoylamino)phenylsulfonyl]glycine (BAPSG), a potent and selective aldose reductase inhibitor capable of delaying the progression of ocular diabetic complications, the objective of this study was to assess its pharmacokinetics. The plasma pharmacokinetics of BASPG was assessed in male Sprague-Dawley rats following intravenous, intraperitoneal and oral routes of administration and its distribution to various tissues including those of the eye was studied following intraperitoneal administration. In addition, rat plasma protein binding of BAPSG was studied using ultracentrifugation method and its ocular tissue disposition was assessed following topical administration in rabbits. Plasma and tissue levels of BAPSG were analysed using an HPLC assay. BAPSG exhibited dose-proportionate AUC 0→∞ (area under the plasma HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript concentration-time curve) following both intravenous and intraperitoneal administration over the dose range (5-50 mg kg −1 ) studied and an erratic oral absorption profile with low oral bioavailability. The fraction bioavailability following oral and intraperitoneal administration was 0.06 and 0.7-1, respectively. BAPSG exhibited short plasma elimination half-lives in the range 0.5-1.5 h. BAPSG was bound to rat plasma proteins and the percent protein binding ranged from 83 to 99.8%. BAPSG was better distributed to cornea, lens and retina than to brain, following intraperitoneal administration in rats. However, the distribution was lower compared with kidney and liver. Following topical administration in rabbits, BAPSG delivery to the surface ocular tissues, cornea and conjunctiva was higher compared with intraocular tissues, aqueous humour, iris-ciliary body and lens. Thus, BAPSG was distributed to ocular tissues following systemic and topical modes of administration.

show abstract

Section: Introductionmentioning

confidence: 99%

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

Sunkara

Ayalasomayajula

Rao

et al. 2004

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

show abstract

“…A number of structurally diverse naturally occurring and synthetic AR inhibitors have been studied in vivo to clarify their effectiveness in the prevention of diabetic complications in experimental animals, 4) as well as in clinical trials. 5) Specific inhibitors of the enzyme may be therapeutically attractive agents for the prevention and/or treatment of diabetic complications. The therapeutic potential of AR inhibitors is manifested by the clinical evaluation of a number of compounds including epalrestat and tolrestat.…”

mentioning

confidence: 99%

Inhibitory Effects of Isorhamnetin-3-O-.BETA.-D-glucoside from Salicornia herbacea on Rat Lens Aldose Reductase and Sorbitol Accumulation in Streptozotocin-Induced Diabetic Rat Tissues

Lee¹,

Lee

Lee³

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The inhibitory effects of compounds from Salicornia herbacea (Chenopodiaceae) on rat lens aldose reductase (RLAR) and sorbitol accumulation in streptozotocin-induced diabetic rat tissues were investigated. The various fractions from the MeOH extract of S. herbacea were tested for their effects on RLAR in vitro. Among them, the EtOAc fraction was found to exhibit a potent RLAR inhibition (IC 50 ‫57.0؍‬ m mg/ml), from which an active principle as a potent AR inhibitor was isolated and its chemical structure was

show abstract

“…De acordo com a classificação de Lemp e colaboradores, o olho seco por déficit androgênico poderia ser incluído entre as deficiências lacrimais não-Sjöegren com doença lacrimal secundária (8) . Em portadores de diabete, a grande prevalência de achados típicos de olho seco tem sido atribuída, principalmente, a uma neuropatia específica (32)(33)(34)(35)(36)(37) , classificada de deficiência lacrimal não-Sjöegren do tipo disfunção reflexa.…”

Section: Classificação Etiológica -Report Of the National Eye Instituunclassified

Olho seco: conceitos, história natural e classificações

Fridman¹,

Freitag²,

Kleinert³

et al. 2004

Arq. Bras. Oftalmol.

View full text Add to dashboard Cite

A disfunção do filme lacrimal, mais conhecida como "olho seco" é, segundo vários autores, uma das condições mais freqüentes na prática oftalmológica (1)(2)(3) . Parece acometer de 15 a 40% da população em geral (4) , sendo as mulheres e os idosos os grupos mais atingidos por esta síndrome (5) . O olho seco costuma provocar queixas que, geralmente, variam de um leve desconforto ocular a uma dor severa e incapacidade em manter os olhos abertos (6)(7)(8)(9)(10) . A morbidade associada à síndrome se relaciona a mudanças na superfície ocular, que dão origem a um espectro de anormalidades que abrangem: erosões superficiais puntiformes, filamentos corneanos, placas mucosas e defeitos epiteliais. Nos casos mais severos, a ocorrência de complicações como as úlceras de córnea pode trazer sérios riscos à integridade ocular (9) . Apesar do grande avanço do conhecimento sobre essa condição nos últimos 25 anos (11) , ainda há pouco consenso entre os principais pesquisadores a respeito de muitos de seus aspectos essenciais. Assim, as manifestações persistentes da síndrome do olho seco, freqüentemente refratárias a tratamentos paliativos, não raramente, se constituem numa grande fonte de frustração, tanto para os pacientes como para seus médicos (12) , que têm dificuldades justificadas para a abordagem do problema. CONCEITOS E DEFINIÇÕES EM OLHO SECOAs dificuldades na avaliação do olho seco se iniciam pelas divergências existentes entre as diversas definições encontradas na literatura.Scarpi sugere que a síndrome está associada a anormalidades na relação entre a produção da lágrima e a manutenção da superfície córneo-conjuntival (13) . Lemp et al propõem que o olho seco, ou ceratoconjuntivite "sicca", é um distúrbio associado a uma deficiência na produção lacrimal e/ou a um excesso em sua evaporação, causando desconforto ocular e danos especialOlho seco: conceitos, história natural e classificações A síndrome do olho seco constitui freqüentemente, grande fonte de frustração, tanto para os pacientes, como para os oftalmologistas que, não raramente, são vencidos pela persistência dos sintomas, apesar dos esforços para sua abordagem diagnóstica e terapêutica. O tema adquire sua real importância quando nos defrontamos com o fato do "olho seco" ser uma das queixas mais comuns na prática oftalmológica. Os autores apresentam uma revisão de aspectos essenciais para a compreensão da moderna abordagem desta síndrome. RESUMODescritores: Síndromes do olho seco; Lágrimas/secreção; Soluções oftálmicas/uso terapêutico; Síndrome de Sjöegren; Glândulas meibomianas ATUALIZAÇÃO CONTINUADA

show abstract

Clinical Trial of an Aldose Reductase Inhibitor in Diabetic Neuropathy

Cited by 66 publications

References 8 publications

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

Systemic and ocular pharmacokinetics of N-4-benzoylaminophenylsulfonylglycine (BAPSG), a novel aldose reductase inhibitor

Inhibitory Effects of Isorhamnetin-3-O-.BETA.-D-glucoside from Salicornia herbacea on Rat Lens Aldose Reductase and Sorbitol Accumulation in Streptozotocin-Induced Diabetic Rat Tissues

Olho seco: conceitos, história natural e classificações

Contact Info

Product

Resources

About