The technique of accelerator mass spectrometry (AMS) was validated successfully and used to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate ...(7-deaza-2'-C-methyl-adenosine; Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across subpharmacological (microdose) and pharmacological dose ranges in an animal model, before initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as liquid chromatography-tandem mass spectrometry and liquid scintillation counting analyses. Compound A displayed multiphasic kinetics and exhibited low plasma clearance (5.8 ml/min/kg), a long terminal elimination half-life (17.5 h), and high oral bioavailability (103%). Currently, there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus subpharmacological doses using microdosing strategies. The present study thus provides the first description of the full pharmacokinetic profile of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A following dosing at 0.02 mg/kg were similar to those at 1 mg/kg, indicating that in the case of Compound A, the pharmacokinetics in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even after a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques.
The disposition of vorinostat, an anticancer agent, was investigated in rats and dogs. Vorinostat possessed high serum clearance, a short elimination half-life and low oral bioavailability in both ...species. The renal route played an important role in the elimination of drug-related material and vorinostat was eliminated primarily by metabolic biotransformation.
The rapidly expanding market for wearable computing devices (wearables), driven by the confluence of information and communication technology and public acceptance of a design aesthetic, suggests ...nearly limitless potential for consumer uses. As adoption of wearables spreads, there are cultural and social impacts that represent both barriers and opportunities, with subsequent public policy ramifications. All too often designers, technologists, and policymakers operate independently; consequently, often products are out of sync, lack interoperability, or are hindered by well-meaning (but obstructive) policy. This article proposes a collaborative policy design framework, based on initial trials undertaken at a multidisciplinary collaborative engineering center, the Wireless Rehabilitation Engineering Research Center. The proposed collaborative policy design process will enhance the development of wearable devices and guide interdisciplinary collaborators as they explore the various implications and effects of device design in social, technological, and regulatory contexts.
Data from 175 accredited programs depicted the state of the art in master's nursing education in the United States in light of projected national trends in the health care delivery system. The ...findings and projected trends derived from the literature formed the basis for recommendations to improve master's programs. (JOW)
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