Current Issue : October - December Volume : 2015 Issue Number : 4 Articles : 5 Articles
Background: Bevacizumab (Avastin�®) is as effective as ranibizumab (Lucentis�®) in the treatment of neovascular\nage-related macular degeneration (nAMD). However it has two important structural differences. First, it has two active\nsites instead of one; second, it retains the Fc portion of the antibody which would be expected to confer a significantly\nlonger half-life. These agents have been associated with systemic complications including strokes, so it is desirable to\nuse the smallest effective dose. Furthermore, the standard dosing regimen requires monthly hospital visits, which\npresent a significant challenge both to the hospital services and to the patients (who are elderly).\nMethods/Design: Patients ?50 years who are eligible for anti-vascular endothelial growth factor (VEGF) treatment of\nnAMD in the NHS, who are either newly referred for treatment or have reactivation of nAMD and who have not received\ntreatment to either eye for the previous six months.\nWe have designed a factorial multi-centre masked randomised controlled trial using bevacizumab as the intervention,\nwith patients randomised to one of four arms: to standard or low dose and to monthly or two-monthly patient review.\nThe aim is to recruit sufficient patients (around 1,000) to obtain 304 patients meeting the endpoint over a four-year\nperiod. The primary endpoint is time to treatment failure to be analysed using Cox regression.\nDiscussion: This randomised control trial will show if half dose and two monthly as required is as effective as full dose\nand monthly regimes. A two monthly as required regimen of Bevacizumab would significantly reduce both the cost\nand the service delivery burden for the treatment of nAMD while a reduced dose would be expected to enhance the\nsafety profile of this treatment regime....
Background: Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and\ndirectly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has\nnot yet been found.\nMethods: In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to\nthe olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically\naccurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on\nthe olfactory delivery efficiency.\nFindings: Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly\nenhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of\nmagnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril\n(i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By\ncombining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more\nthan 90% were observed as compared to the extremely low olfactory dosage (,1%) with conventional inhaler devices.\nConclusion: Results of this study have important implications in developing personalized olfactory delivery protocols for the\ntreatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different\npointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery....
Setting: In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in\nthe dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose\ncombination tablets.\nObjective: To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the\ntreatment of childhood tuberculosis.\nDesign: Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid\nchromatography. The content uniformity was assessed by comparing drug content measured in split portions with their\nexpected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets.\nResults: All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and\nthird portions was found outside the tolerated variation range and the split formulation failed the requirements for content\nuniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used\nbut this did not improve the findings.\nConclusion: In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is\nan absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis....
Artemisinin-based combination therapies (ACTs) are the cornerstone for the treatment of malaria. However, confirmed\nresistance to artemisinins in South-East Asia, and reports of reduced efficacy of ACTs raise major concerns for malaria\ntreatment and control. Without new drugs to replace artemisinins, it is essential to define dosing strategies that\nmaximize therapeutic efficacy, limit the spread of resistance, and preserve the clinical value of ACTs. It is important to\ndetermine the extent to which reduced efficacy of ACTs reflects true resistance versus sub-optimal dosing, and quantify\nother factors that determine treatment failure. Pooled analyses of individual patient data from multiple clinical trials, by\ninvestigators in the Worldwide Antimalarial Resistance Network, have shown high overall efficacy for three widely used\nACTs, artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine. Analyses also highlight\nthat suboptimal dosing leads to increased risk of treatment failure, especially among children. In the most recent\nstudy, an analysis of clinical trials of artesunate-amodiaquine, widely used among children in Africa, revealed a\nsuperior efficacy for fixed-dose combination tablets compared to loose non-fixed dose combinations. This highlights\nthe benefits of fixed-dose combinations as a practical strategy for ensuring optimal antimalarial dosing and\nmaximizing efficacy....
Introduction: Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007\nPaediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric\nInvestigation Plans (PIPs) are subject to agreement by the European Medicines Agency (EMA) and its Paediatric Committee\n(PDCO). The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the\nchanges implemented as a result of the EMA/PDCO review.\nMethods: All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if\nthey contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic\narea (EMA classification system); target age range (as defined by industry) and pharmaceutical characteristics (active\nsubstance, dosage form(s) as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage\nform) was extracted from the EMA website or the EMA/PDCO assessment reports.\nResults: A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431\nstrengths/compositions. Eighty-two PIPs (37%) included tablets, 44 (20%) liquids and 35 (16%) dosage forms with a specific\ncomposition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review\nresulted in an increase of 13 (207 to 220) oral paediatric dosage forms and 44 (387 to 431) dosage forms with a specific\ncomposition/strength. For many PIPs, the target age range was widened and the excipient composition and usability\naspects modified.\nConclusion: The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage\nforms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger\nchildren. Changes to their pharmaceutical design were less profound....
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