Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of AS-013, a Prostaglandin E
            <sub>1</sub>
            Prodrug, in Patients With Intermittent Claudication

Belch, J J F; Bell, Patrick; Creissen, D.; Dormandy, J. A.; Kester, R. C.; McCollum, Regina; Mizushima, Yutaka; Ruckley, C. V.; Scurr, J. H.; Wolfe, John H.

doi:10.1161/01.cir.95.9.2298

Cited by 68 publications

(27 citation statements)

References 12 publications

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“…In a smaller placebo-controlled study, a PGE 1 prodrug induced short-term, dose-related increases in both pain-free and max-imal walking distances. 22 In a small, uncontrolled study, 23 a 7-day infusion of PGE 1 increased resting calf and skin blood flows compared with baseline but left the ABI unchanged. It seems, therefore, that oral BPS and intravenous PGE 1 have comparable effects on walking distances.…”

Section: Discussionmentioning

confidence: 99%

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Oral Beraprost Sodium, a Prostaglandin I ₂ Analogue, for Intermittent Claudication

et al. 2000

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Background-Beraprost sodium (BPS) is a new stable, orally active prostaglandin I 2 analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication. Methods and Results-Patients (nϭ549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by Ͻ25% were then randomized to receive either BPS (40 g TID, nϭ209) or placebo (nϭ213) in a double-blind manner for 6 months. Pain-free and maximum walking distances were measured on the occasion of treadmill exercise tests performed at baseline and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an improvement of Ͼ50% in pain-free walking distance at month 6 and in Ն1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, Pϭ0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups (Pϭ0.001) and maximum walking distances by 60.1% and 35.0%, respectively (Pϭ0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group. Conclusions-These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication.The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials. Key Words: claudication Ⅲ beraprost sodium Ⅲ prostaglandins I ntermittent claudication is a common presentation of lower-limb arterial disease, with a prevalence of 1% to 7% in men 50 to 75 years old. 1,2 Medical therapy for patients with intermittent claudication has 2 goals: improvement of symptoms and prevention of cardiovascular events. Many agents, including vasodilators, have been tried for the relief of symptoms, although their effectiveness is still subject to debate. The antiplatelet and vasodilating properties of epoprostenol (prostaglandin [PG] I 2 ) make it a theoretically interesting agent in the treatment of peripheral vascular disease. 3 Although promising results were reported for its use in the treatment of intermittent claudication, 4 its very short half-life and high chemical instability precluded its use as a therapeutic agent and led to the development of more stable synthetic analogues. Iloprost, to date the most extensively studied of these analogues, has been shown to provide pain relief and to accelerate ulcer healing in patients with stage III or IV critical leg ischemia 5 and has been licensed in some countries for the treatment of thromboangiitis obliterans. The need for an intravenous infusion of iloprost, although acceptable for the treatment of critical ischemia, makes it unacceptable for the long-term treatment of intermittent claudication.Beraprost sodium (BPS) is a new stable, orally active PGI 2 analogue with antiplatelet and vasodilating prope...

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Section: Discussionmentioning

confidence: 99%

“…[21][22][23] The largest published study 21 evaluated 213 patients with a maximum walking distance of 50 to 200 m at treadmill exercise. PGE 1 was infused 5 days a week for 4 weeks.…”

Section: Discussionmentioning

confidence: 99%

Oral Beraprost Sodium, a Prostaglandin I ₂ Analogue, for Intermittent Claudication

et al. 2000

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“…139 A substituição da PGE1 por seu pró-fármaco AS013 resultou em maior estabilidade química do fármaco na emulsão e, assim, em um efeito mais prolongado. 133,140 Outras nanoemulsões de PGE1 contendo óleo de oliva como núcleo oleoso também já estão disponíveis comercialmente no Japão (Alyprost ® , Nippon Chemiphar, e Prink ® , Taiyo Yakuhin). 138 Apesar de todos os estudos em andamento, a nanoemulsão originalmente desenvolvida ainda é clinicamente muito vantajosa, sendo o tratamento de escolha para diversas patologias.…”

Section: Prostaglandina Eunclassified

Nanoemulsões como sistemas de liberação parenteral de fármacos

Bruxel¹,

Laux²,

Wild³

et al. 2012

Quím. Nova

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Recebido em 20/10/11; aceito em 29/3/12; publicado na web em 3/7/12 NANOEMULSIONS AS PARENTERAL DRUG DELIVERY SYSTEMS. Lipid nanoemulsions have recently been proposed as parenteral delivery systems for poorly-soluble drugs. These systems consist of nanoscale oil/water dispersions stabilized by an appropriate surfactant system in which the drug is incorporated into the oil core and/or adsorbed at the interface. This article reviews technological aspects of such nanosystems, including their composition, preparation methods, and physicochemical properties. From this review, it was possible to identify five groups of nanoemulsions based on their composition. Biopharmaceutical aspects of formulations containing some commercially available drugs (diazepam, propofol, dexamethasone, etomidate, flurbiprofen and prostaglandin E1) were then discussed.Keywords: emulsion; parenteral; drug. INTRODUÇÃOA solubilização de fármacos de reduzida hidrossolubilidade visando sua administração parenteral representa um grande desafio na área de desenvolvimento de medicamentos. Diversas estratégias são descritas na literatura para esta finalidade, incluindo a modificação do pH do veículo, a adição de cossolventes ou, ainda, a formação de complexos de inclusão com ciclodextrinas.1 Entretanto, limitações relacionadas à biocompatibilidade dos adjuvantes empregados, aos relatos de dor e de possível precipitação dos fármacos durante a administração podem ser considerados como fatores limitantes do uso destas abordagens. Neste contexto, sistemas nanoestruturados têm se mostrado promissores. Nanoemulsões lipídicas óleo em água têm sido empregadas há mais de 40 anos como fonte de calorias e ácidos graxos essenciais 2 e, mais recentemente, como sistemas de liberação de fármacos. A biocompatibilidade das matérias-primas empregadas para a sua obtenção (óleos de origem natural ou semissintética e fosfolipídeos) torna estes sistemas uma alternativa promissora para a administração de diversos tipos de moléculas.3 Nanoemulsões podem ser definidas como sistemas heterogêneos nos quais um líquido (a fase interna) é disperso em outro (a fase externa) na forma de gotículas, na presença de um agente emulsionante. Suas propriedades físico--químicas, influenciadas pela composição quali-e quantitativa e pelas condições de preparação, devem ser estritamente controladas, visando a administração por via parenteral e a estabilidade do sistema. 4,5 Existem na literatura algumas inconsistências relacionadas aos conceitos de nanoemulsões em relação às microemulsões. Apesar destes sistemas poderem apresentar características estruturais e visuais semelhantes em determinadas condições, diferenciam-se quanto a estabilidade termodinâmica. Contrariamente às nanoemulsões, as microemulsões são sistemas termodinamicamente estáveis. Entretanto, podem apresentar limitações para administração por via parenteral, pois suas propriedades são fortemente afetadas por alterações de temperatura e/ou diluições. Apesar da nomenclatura empregada, microemulsões apresentam geralmente tamanho...

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“…Results from a number of clinical and animal studies support this notion (3)(4)(5). However, the range of activities of PGE 1 are also related to adverse effects (such as hypotension and diarrhea) due to its distribution throughout the body when administered systemically (4,6). Furthermore, in addition to its chemical instability (hydrolysis to PGA 1 ), PGE 1 is easily inactivated by 15-hydroxydehydrogenase during the passage through the lung (7)(8)(9).…”

Section: Introductionmentioning

confidence: 97%

Synthesis of Prostaglandin E1 Phosphate Derivatives and Their Encapsulation in Biodegradable Nanoparticles

et al. 2009

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Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of AS-013, a Prostaglandin E ₁ Prodrug, in Patients With Intermittent Claudication

Cited by 68 publications

References 12 publications

Oral Beraprost Sodium, a Prostaglandin I ₂ Analogue, for Intermittent Claudication

Oral Beraprost Sodium, a Prostaglandin I ₂ Analogue, for Intermittent Claudication

Nanoemulsões como sistemas de liberação parenteral de fármacos

Synthesis of Prostaglandin E1 Phosphate Derivatives and Their Encapsulation in Biodegradable Nanoparticles

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Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of AS-013, a Prostaglandin E 1 Prodrug, in Patients With Intermittent Claudication

Cited by 68 publications

References 12 publications

Oral Beraprost Sodium, a Prostaglandin I 2 Analogue, for Intermittent Claudication

Oral Beraprost Sodium, a Prostaglandin I 2 Analogue, for Intermittent Claudication

Nanoemulsões como sistemas de liberação parenteral de fármacos

Synthesis of Prostaglandin E1 Phosphate Derivatives and Their Encapsulation in Biodegradable Nanoparticles

Contact Info

Product

Resources

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Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of AS-013, a Prostaglandin E ₁ Prodrug, in Patients With Intermittent Claudication

Oral Beraprost Sodium, a Prostaglandin I ₂ Analogue, for Intermittent Claudication

Oral Beraprost Sodium, a Prostaglandin I ₂ Analogue, for Intermittent Claudication