Untitled

Abstract

Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h at zero-order rate. In a pilot experiment in two subjects it was shown that lidocaine administration close to the anus for 5 h resulted in higher lidocaine plasma levels as compared to administration at 15 cm from the anus. Six other subjects participated in three separate experiments, in which lidocaine was administered rectally close to the anus and at 7.5 and 15 cm from the anus. A zero-order infusion plasma level profile was found for both the parent compound and its metabolite. The MEGX/lidocaine plasma concentration ratio was calculated for all experiments. After administration most proximal to the anus the mean metabolite/parent drug concentration ratio was significantly less than that obtained after administration at 15 cm from the anus, whereas at approximately 7.5 cm from the anus the values were in-between. Comparison of the AUC lidocaine/AUC MEGX ratios gave similar results; the highest value, 3.2 ± 1.3 (mean ± S. D.), was found after administration close to the anus, while at 15 cm from the anus the ratio was 1.6 ± 0.3 (p < 0.01). The terminal elimination half-lives of lidocaine and MEGX did not differ for the three sites of administration, and the mean values were 110 and 180 min respectively. The results of this study demonstrate that the site of drug administration in the human rectum determines the degree of hepatic "first-pass" elimination of high-clearance drugs. Maximal avoidance of presystemic elimination is achieved when administration takes place close to the anus.

Barriers and Facilitators of Collaborative Management in Technological Innovation Projects

“…Farias et al (2006) present Clark and Wheelwright's (1995) typology about problematic and successful projects, in which they evidence sharing, a systemic approach, team responsibility and the role of leadership, among other characteristics of a successful project. In the international literature, there are some studies which posit people as being the differential for attaining innovation (ALIAGA, 2005;Leede;Looise, 2005;Ekvall, 1996).…”

“…It proposes integration between policies and people management practices, considering multidimensional models that evidence certain organizational characteristics inherent to the context and which contribute to results in innovation, including creativity as the input and output of the process (FERRIS et al, 1999;Albuquerque, 2002;Dutra, 2002;Laursen;Foss, 2003;Aliaga, 2005;Leede;Looise, 2005;Martin-Alcazar Et Al, 2005;Albuquerque, 2010). Regarding the barriers and facilitators to creativity in the organizational environment, there are groups of variables based on several studies, especially those in Amabile's researches (1998), which consider encouraging creativity, the task environment as well as resources and organizational hindrances (PAROLIN; Albuquerque, 2010).…”

“…Therefore, the first activity undertaken by innovative companies is executed by their human resources, which must interact and act coherently (ALIAGA, 2005;Leede;Looise, 2005).…”

“…The creativity perceived as input and output to the innovation management process needs to be fed in the organizational context, through policies and actions which ascertain that people are the differential for achieving results with innovation (ALBUQUERQUE, 2002;Leede;Looise, 2005;Aliaga, 2005;Albuquerque, 2010).…”

“…Farias et al (2006) present Clark and Wheelwright's (1995) typology about problematic and successful projects, in which they evidence sharing, a systemic approach, team responsibility and the role of leadership, among other characteristics of a successful project. In the international literature, there are some studies which posit people as being the differential for attaining innovation (ALIAGA, 2005;Leede;Looise, 2005;Ekvall, 1996).Another important observation regarding the tendency towards development of innovation projects in collaborative networks is noted by Enkel et al (2009). The author emphasizes that it is less important for companies to have a central laboratory (close innovation) when external knowledge is available.…”