Dopamine agonists Sample Clauses

Dopamine agonists. Due to the difficult permeability properties of the skin, the choice of potential candidates of dopamine agonists for passive transdermal delivery is limited. In order to penetrate the skin, the permeant should be potent, since the relative bioavailability is low and should have specific physicochemical properties: moderate hydrophilicity and low molecular weight (<500 Mw). Despite these restrictions several molecules have been investigated for the symptomatic treatment of Xxxxxxxxx’x disease with transdermal passive delivery. All the DA of which the feasibility of (passive and/or iontophoretic) transdermal delivery has been investigated together with the structure of levodopa are depicted in Figure 3. In the 1980’s naxagolide was identified as a very potent dopamine agonist and a potential candidate for transdermal delivery due to its moderate lipophilic nature. Despite the very promising results that were obtained in vitro and later in vivo in primates and humans [69-70], the further development was discontinued because of the lack of efficacy as monotherapy and concerns about the toxicity [71]. These results encouraged further investigations with other potential candidates. A number of gel formulations for bromocriptine, an ergot derived dopamine agonist, were developed and transdermal delivery was compared with oral delivery in rabbits. It was observed that a gel, formulated with chitosan showed similar plasma concentration profile as with a commercially available tablet [72]. An enhancement in transdermal transport in vitro of pergolide, another ergot derived dopamine agonist, was obtained using elastic vesicles, but further investigation in vivo is necessary [73]. Transdermal delivery of a third ergot derivative dopamine agonist, lisuride showed promising efficacy as add-on therapy for Pd. Axxonis Pharma, a pharmaceutical company in Germany, recently submitted a European marketing authorization application for the transdermal patch and subcutaneous infusion of lisuride [50, 74]. The non-ergot derivatives, such as piribedil, apomorphine and rotigotine do not cause serious fibrotic reactions, associated with the use of the older ergot-derived compounds, described above. For this reason the non-ergot derivatives are the preferred dopamine agonists to commence therapy, especially in younger patients [1]. A randomized double blind clinical study, including 72 patients with Pd, failed however to show clinical efficacy of transdermal delivery of piribedil, ...
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Dopamine agonists. Transdermal iontophoresis of various non-ergot dopamine agonists have been studied in vitro and in vivo for symptomatic treatment of Pd. Several studies on the transdermal iontophoretic delivery of R-apomorphine have been reported. After promising results in vitro across human skin [112], in small scale clinical studies apomorphine was applied using transdermal iontophoresis in patients with Pd. After application of 2 different current densities (250 and 375 μA.cm-²) for 1 hour, in all patients measurable plasma concentrations were observed. However these plasma levels were subtherapeutic in all patients, except one [113]. Xx et al. showed an improvement of the transdermal iontophoretic delivery of this dopamine agonist after non-occlusive pretreatment of the skin with a surfactant formulations [114]. A 2-fold and 1.4 fold increase in flux was observed in studies across HSC and dermatomed human skin (DHS), respectively [115]. These findings led to further exploration of the feasibility of the transdermal iontophoretic delivery of apomorphine in a clinical study including 16 patients. 2 groups of patients were compared receiving R- apomorphine using transdermal iontophoresis (250 μA.cm-², 3 hours) with or without pretreatment of with the surfactant formulation, respectively. With a similar enhancement ratio (1.3 times) as was observed for transport across DHS, the surfactant pretreatment increased the iontophoretic delivery. In this study 62.5% and 37.5% respectively, of the surfactant pretreated and control group, reported clinical improvement [116]. The feasibility of transdermal iontophoretic administration of ropinirole was explored, because of its suitable fysicochemical properties (Mw: 260.4 g.mol-1; pKa:
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Dopamine agonists. Fibrate products.
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Related to Dopamine agonists

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