ABSTRACT
Generic substitution of narrow therapeutic index drugs can have unintended consequences. Generic switching is often driven by cost incentives, regulations and supply, but may raise concerns about equal bioavailability, therapeutic equivalence and about possible confusion for the patient. Integrated systems of care with active management of patient behaviors, including adherence, may minimize the impact of switching. This article is intended to present policy drivers and potential consequences of generic switching and the role of pharmacist education in minimizing patient risk using warfarin and the pharmaceutical distribution systems of the United States and Germany as examples.
Subject(s)
Drug Substitution , Drugs, Generic/standards , Legislation, Drug , Therapeutic Equivalency , Treatment Outcome , Anticoagulants/adverse effects , Anticoagulants/standards , Biological Availability , Drug Industry/economics , Drug Industry/trends , Drugs, Generic/economics , Germany , Guidelines as Topic , Humans , Policy , United States , Warfarin/adverse effects , Warfarin/standardsABSTRACT
Since oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD) and since the age-adjusted incidence of AD is higher in females than males, we examined a possible influence of gender on antioxidant metabolism in brains from male and female AD patients and age-matched controls. Activities of copper/zinc-dependent superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-disulfide reductase (GR) were elevated in AD samples compared to controls. Upon in vitro stimulation, levels of malondialdehyde formation were significantly lower in AD samples, probably due to the increased antioxidant capacity. Overall, our results indicate that antioxidant metabolism is functionally still intact but increased in AD implying that oxidative damage is caused rather by overproduction than by insufficient detoxification of ROS. Among AD patients, a gender-specific partial upregulation of antioxidant defence was present: activities of SOD and GPx were even further increased in female patients, and levels of 4-hydroxynonenal, a marker of oxidative damage, were higher than in male patients. Importantly, our results are in line with epidemiological studies indicating a higher risk for AD in females. Thus, gender differences in oxidative stress parameters might be related to the higher prevalence of AD in females.
Subject(s)
Alzheimer Disease/enzymology , Antioxidants/metabolism , Genetic Predisposition to Disease/genetics , Oxidative Stress/genetics , Sex Characteristics , Up-Regulation/genetics , Aged , Aldehydes/metabolism , Alzheimer Disease/genetics , Brain/enzymology , Brain/physiopathology , Female , Glutaredoxins , Glutathione Peroxidase/metabolism , Humans , Lipid Peroxidation/genetics , Male , Malondialdehyde/metabolism , Protein Disulfide Reductase (Glutathione)/metabolism , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
The aim of this paper is to prepare and stabilise, in situ, colloidal microsuspensions of triclosan using the polymer, hydroxypropyl methylcellulose (HPMC). The suspensions were prepared from supersaturated solutions of triclosan. The cosolvent technique was used to create supersaturation. Propylene glycol and water were used as the cosolvents. The triclosan particles had a large needle-shaped morphology, when grown in the absence of the polymer. Moreover, the particles grew rapidly to sizes greater than 5 micrometer over a period of 7h. When HPMC was added, the particle sizes were in the range 90-250 nm depending on the amount of polymer present in the solutions. The stability of the solutions was evaluated over a period of 40 days during which the particle sizes did not vary. The results were consistent with the mechanism proposed by Raghavan et al. [Int. J. Pharm. 212 (2001b) 213].
