Preclinical absorption, distribution, metabolism, and excretion of an oral amide prodrug of gemcitabine designed to deliver prolonged systemic exposure.

Gemcitabine is an intravenously administered nucleoside analog chemotherapeutic agent. The ability to deliver this agent as an oral drug would allow greater flexibility of administration and patient convenience; however, attempts have been fraught with high first-pass metabolism and potential intestinal toxicity. Alternatively, an amide prodrug of gemcitabine (LY2334737) was discovered, which is able to avoid the extensive first-pass metabolism that occurs following administration of gemcitabine. Preclinical in vitro and in vivo experiments were conducted to evaluate the hydrolysis and pharmacokinetics of LY2334737 and its downstream metabolites. In mice, rats, and dogs, the prodrug is absorbed largely intact across the intestinal epithelium and delivers LY2334737 to systemic circulation. The hydrolysis of LY2334737 is relatively slow, resulting in sustained release of gemcitabine in vivo. In vitro experiments identified carboxylesterase 2 (CES2) as a major enzyme involved in the hydrolysis of LY2334737, but with relatively low intrinsic clearance. Following hydrolysis of the prodrug, gemcitabine is cleared predominantly via the formation of its inactive metabolite dFdU. Both biliary and renal excretion was responsible for the elimination of LY2334737 and its metabolites in both mice and dogs.

E-health and the Universitas 21 organization: 2. Telemedicine and underserved populations.

Telemedicine activities in underserved communities were reviewed as part of the Universitas 21 (U21) e-health project. A SWOT analysis (strengths, weaknesses, opportunities, threats) was conducted on 12 articles identified in a literature review, supplemented by expertise from U21 members. The analysis showed that threats include the reluctance of populations to use telemedicine services, and a general absence of infrastructure and resources to sustain them. Opportunities centre around potential research, including cost-effectiveness analyses and quantitative assessments of existing telemedicine services. The great strength of telemedicine is that it can improve access to health services among those most in need. However, its greatest weakness is the lack of evidence supporting its clinical and cost advantages relative to traditional services. This represents an important opportunity for research on telemedicine initiatives among underserved populations.