Drug Targeting to the Lung: Chemical and Biochemical Considerations
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Fluticasone propionate (28) and mometasone furoate (29) have both been formulated for use in asthma (Bernstein et al. 1999). Many of the adverse effects of elevated systemic glucocorticoid levels have been reduced through the use of inhalation as a method of drug delivery (Barnes et al. 1998). Inhalation therapy targets the local affected area, where it maximizes local efficacy, while reducing systemic bioavailability. Therefore, at therapeutic doses of inhaled glucocorticoids, the risk of systemic effect is considerably reduced when compared to oral glucocorticoid therapy. Mometasone furoate (29) is a synthetic glucocorticoid that is structurally similar to the adrenocorticosteroids and prednisolone. The structure was designed to optimize potency; the furoate group at position C17 greatly increases lipid solubility, while the 21-chloromoiety is important for maximum potency and topical activity (Onrust and Lamb 1998).
Topical Corticosteroids
John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Mark G. Lebwohl in Mild to Moderate Psoriasis, 2014
Improving the safety profile of topical corticosteroids while maintaining potency has proven elusive. Creating nonfluorinated potent corticosteroids is not the solution; it is the strength of the corticosteroid, not the fluorine atom covalently bound in the molecule, that contributes to adverse events. There is no reason whatsoever to expect that potent nonfluorinated corticosteroids will have fewer or less severe side effects than fluorinated corticosteroids of equal potency. Mometasone furoate uses chlorination rather than fluorination to achieve potency. Some studies claim a reduced risk of adverse effects with mometasone furoate [32,49]. These studies, however, were not adequately designed to demonstrate comparable potency while decreasing adverse event rates. For example, one study comparing mometasone to hydrocortisone found greater potency with mometasone but not significantly greater adverse events; this study was powered to find differences in efficacy but was not powered to identify the likely real differences in adverse event profiles [50]. Studies of the nonfluorinated prednicarbate have also claimed a dissociation between benefit and risk. Although both a reduction in adverse effect rate and equal potency have been demonstrated independently [34,35,51,52], studies have not shown the occurrence of both outcomes simultaneously under identical conditions. Therefore, we conclude that the existence of safer topical corticosteroids with equal potency is yet to be demonstrated.
Statistical Methods for Assessment of Complex Generic Drugs
Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow in Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
BE studies with clinical endpoints are relatively expensive and require large numbers of subjects. Therefore, if there exist acceptable PK or PD endpoints, these endpoints can be preferred. For instance, for topical dermatologic corticosteroid drug products, BE can be established using in vivo PD studies. The PD endpoint for dermatologic corticosteroid drug products is obtained through the McKenzie-Stoughton Vasoconstrictor Assay (VCA) approach (Smith et al., 1993). The VCA approach is based on the fact that a corticosteroid product will cause vasoconstriction of the skin microvasculature and consequently will produce a visible blanching response over time. Note that the VCA approach is limited only to dermatologic corticosteroid drug products. Mometasone furoate cream is a representative of this category. For BE assessment of mometasone furoate cream, both a pilot and pivotal vasoconstrictor study are recommended. The aim of the pilot study is to determine the appropriate dose duration for use in the subsequent pivotal BE study (US FDA, 2016c).
Safety review of current systemic treatments for severe chronic rhinosinusitis with nasal polyps and future directions
Published in Expert Opinion on Drug Safety, 2021
Biological agents are medicines produced by a biological process. Monoclonal antibodies (mAB) are one type of biologic that are becoming more widely used in the treatment of inflammatory conditions where pharmacological therapy does not provide adequate symptom control. They target specific inflammatory mediators or immune cells in the pathophysiological pathways that produce chronic inflammatory diseases [99]. Studies have evaluated mAB in conditions such as asthma and atopic dermatitis leading to increasing interest that these agents may also offer some benefit in treating patients with CRSwNP. All currently available biologics used in the treatment of CRSwNP are given by injection. It should also be noted that biologics are considered as an add-on treatment for severe CRSwNP, given in addition to an intranasal corticosteroid. In all trials discussed below, mometasone furoate spray was given as a maintenance treatment in both active and placebo treatment arms and therefore adverse events may be attributable to this in both arms.
Topical prebiotics/postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients
Published in Journal of Dermatological Treatment, 2023
Carlo Gelmetti, Corinna Rigoni, Alessandra Maria Cantù, Antonina Agolzer, Alice Agrusa, Michela Brena, Federica Dall’Oglio, Patrizia Demichelis, Sandra Farina, Lucretia Adina Frasin, Sandra Lorenzi, Giuseppina Mazzola, Marisa Praticò, Stefania Robotti, Aurora Tedeschi, Lucia Villa, Prodromos Ananiadis, Eirini Arkoumani, Iulia Astashonok, Eulalia Baselga Torres, Sidita Borici, Elna Cano, Rozana Cela, Amarda Cengo, Francisca Corella, Xavier Cubiro Raventos, Miriam America De Jesus Silva, Ermira Demiraj, Entela Dhima, Xhiljola Doci, Anna Domarad, Marina Didyk, Albana Dyli, Ourania Efthimiou, Georgia Filippi, Víctor-Adrian Flores Climente, Maria Pilar Garcia Muret, Javier Garcia Navarro, Migena Gega, Aristea Noura Giakoub, Vasileios Giakoubis, Amarda Gica, Marjeta Gjomema, Blerina Guri, Elmijola Janushaj, Antonios Kanelleas, Georgia Kanelopoulou, Entela Kapaj, Dorothea Kapoukranidou, Konstantina Karadima, Athina Katsavou, Lena Kotrulja, Aikaterini Kyriakou, Georgios Larios, Anna Lopez, Cristina Lopez, Sofia Magdalini Manoli, Tatiana Matvienko, Liljana Mervic, Konstantinos Mileounis, Diana Muja, Milkota Nadezhda, Despoina Panagioti, Markos Papakonstantis, Maria Papanikou, Despoina Papathemeli, Kyriaki Papigkioti, Violetta Pivak, Driada Preza, Esther Roé, Mirjam Rogl Butina, Esther Serra Baldrich, Dimitrios Sgouros, Aleksandra Shilova, Eljona Shllaku, Nikolaos Sideris, Ermal Sina, Ardiana Sinani, Fani Sourli-Chasioti, Mirsa Stankaj, Dimitra Tasioula, Athanasios Tsalmadoupis, Fragkiski Tsatsou, Eftichia Tsenebi, Anastasia Tsitlakidou, Politimos Vassis, Eva Vilarrassa, Olga Vorobey, Nikolaos Voutsakis, Svetlana Yakovleva, Svetlana Yakubovskaya, Ekaterina Yerygina, Alexios Zarras, Valbona Zenelaj, Olga Zenko
About 402 subjects, enrolled in 8 European countries, were involved in the study and followed over time for approximately 3 months. After the data-cleaning phase, 6 subjects (1.5%) were excluded from the analysis because they lacked information at baseline. The study is therefore based on a total of 396 subjects of both sexes suffering from Atopic Dermatitis defined according to Hanifin and Rajka’s criteria and recruited from the following countries indicated in Table 2 who met the following inclusion criteria were studied:Male and female sex.Mild and/or moderate AD according to the SCORAD index (9).Patients who may use topical treatment, preferably with mometasone furoate 0.1% cream as needed.Signature of informed consent to participate in the study.
History of asthma in Canada
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2022
The 1970s saw important advances in the modernization of ambulatory asthma treatments. New agents released in the 1970s in the United Kingdom included inhaled disodium cromoglygate (DSCG), a mast cell stabilizer and inhibitor of both allergen- and exercise-induced bronchospasm,52 inhaled salbutamol, a selective ß2 adrenergic agonist considered at that time to be long acting (compared to epinephrine and isoproterenol),53 and inhaled beclomethasone dipropionate (BDP), the first widely used ICS;54 a pMDI containing dexamethasone (alone or combined with isoproterenol) inhaler55 was available in the 1960s but offered little safety advantage over oral dexamethasone and was soon abandoned. Approximate dates of release in Canada were DSCG 1971 (1968 in the United Kingdom and 1985 in the United States50), salbutamol 1972 (1969 in the United Kingdom and 1981 in the United States) and BDP 1978 (1972 in the United Kingdom and 1982 in the United States50). Additional inhaled ß2 agonists include terbutaline (1988) another SABA and the long acting ß2 agonists (LABAs) salmeterol (1994), formoterol (2000) and vilanterol (2015), the former two also available in combination with an ICS (1999, 2002) and the latter only available in a combination inhaler. Six more ICS preparations are now available in Canada: budesonide (1991), fluticasone propionate (1995), BDP-HFA (2000) mometasone furoate (2000), ciclesonide (2006) and fluticasone furoate (FF) (2015). Mometasone furoate is also available in combination with formoterol (2011) and indacaterol (2020).
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