1. UK-343,664 is a potent and specific PDE5 inhibitor. Following single oral doses to human volunteers, it exhibited non-proportional pharmacokinetics over the dose range 30-800 mg. Over this 27-fold dose range, Cmax and AUCt increased 247- and 287-fold respectively. The half-life (4-6 h) was similar at all doses. No systemic exposure was quantifiable at doses <10 mg. 2. UK-343,664 is a lipophilic molecule (log D7.4 = 3.1) and as such is expected to be cleared mainly by metabolism. Based on studies with expressed human P450 enzymes it was concluded that the metabolism of UK-343,664 was predominantly mediated by CYP3A4. With a moderate Km = 76 microM for this enzyme, saturation of first-pass metabolism alone was considered unlikely to account for the non-proportional pharmacokinetics. 3. UK-343,664 showed high affinity for P-glycoprotein in vitro, with a Km = 7.3 microM. In transport studies in LLC-PK1 cell monolayers transfected with P-glycoprotein, UK343,664 showed marked polarized transport which was concentration dependent. 4. The high affinity of UK-343,664 for P-glycoprotein is considered to be the primary source of the non-proportional pharmacokinetic profile observed in man.

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The purpose of this article is to provide education to the RN regarding pressure ulcer prevention and best practice interventions. This investigation focuses on the definition of a pressure ulcer, risk factors for pressure ulcers, and the benefits and importance of using unlicensed assistive personnel to help prevent pressure ulcers. A comprehensive literature review was completed using the Texas Woman's University Library, the Texas Christian University Library, and the World Wide Web. The search engine used was Google. The databases included were CINAHL, Academic Search Complete, Cochrane Library, MEDLINE, and ProQuest Nursing & Allied Health Source. The literature was current, defined as from the last 10 years, and the primary language searched was English. Full-text articles from these databases were included as well as print publications from the university collections. The key search terms from the literature review included (a) pressure ulcer, (b) prevention, (c) unlicensed assistive personnel, (d) nursing assistant, (e) theory of nursing knowledge, (f) incidence, (g) prevalence, (h) Braden scale, (i) moisture, and (j) repositioning. Best practice guidelines were reviewed via the Joanna Briggs database, National Guideline Clearinghouse, Cochrane Library, the Centers for Medicare & Medicaid Services, and the National Institutes of Health. Literature was synthesized to define evidence-based practices that would justify the use of unlicensed assistive personnel for the prevention and care of pressure ulcers.