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General Psychiatry 2019年第6期32卷 293-294页

作者： nicole J leblanc Luana Marques Department of Psychiatry Massachusetts General Hospital Boston Massachusetts USA Harvard Medical School Boston Massachusetts USA

Despite ongoing research on the aetiology,phenomenology and treatment of anxiety disorders,these conditions continue to afflict myriads of individuals *** estimated 11.6%of the global population meets criteria for an anxiety disorder each year,1 and individuals with anxiety disorders experience both functional impairment2 and increased risk for physical health problems.3 In addition to the personal suffering associated with anxiety disorders,these conditions lead to considerable costs for society,including medical expenditures and lost work productivity.4 Moreover,although efficacious interventions for anxiety disorders are available,many individuals do not respond to these treatments5 or struggle to access evidence-based care.6 Thus,much work remains to be done to reduce the global burden of anxiety disorders.

关键词： impairment treatment etiology

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Transdermal Formulation Development and Topical Administration of Atenolol to Cats

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Pharmacology & Pharmacy 2020年第3期11卷 39-53页

作者： Sumeia M. Mohamed John Mark Christensen nicole leblanc Department of Pharmaceutical Science College of Pharmacy Oregon State University Corvallis OR USA Department of Cardiology College of Veterinary Medicine Oregon State University Corvallis OR USA

Atenolol diffusion through synthetic membrane, cloned human epidermis, and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl isosorbide (DMI) were added to the topical formulations and tested for their ability to enhance drug permeation through the test membranes. Topical formulation with penetration enhancers showed a rapid burst of atenolol diffusion for the first two hours (35.5 to 40 μg/ml) followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test membranes. Increased atenolol flux through different test membranes was greatest for synthetic membrane. The topical application of the optimized atenolol formulation to cat skin containing permeation enhancers aided transdermal atenolol drug delivery to treat cats with hypertrophic obstructive cardiomyopathy. The optimum topical formulation demonstrated two fluxes through cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1, and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum atenolol levels (260 ng/ml) for at least one time point. Five of 7 cats had therapeutic serum atenolol concentrations 3 hours post-atenolol. At the 6 hours post-atenolol time point, only 2 had a therapeutic serum atenolol concentration while at 12 hours post-atenolol dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal atenolol administered at 25 mg q12h resulted in clinically therapeutic serum atenolol concentrations in the majority of healthy cats. The optimum transdermal formulation enabled good drug delivery feasible for transdermal application in a clinical trial in cats.

关键词： Atenolol Transdermal Delivery Formulation Cats

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