A phase 1/1b study of PUR1900, an inhaled formulation of itraconazole, in healthy volunteers and asthmatics to study safety, tolerability and pharmacokinetics.

AIMS: Oral itraconazole has variable pharmacokinetics and risks of adverse events associated with high plasma exposure. An inhalation formulation of itraconazole (PUR1900) is being developed to treat allergic bronchopulmonary aspergillosis, an allergic inflammatory disease occurring in asthmatics and patients with cystic fibrosis. METHODS: A 3-part, open-label Phase 1 study was conducted to evaluate safety, tolerability and pharmacokinetics of PUR1900. Healthy volunteers (n = 5-6/cohort) received either single (Part 1) or multiple (Part 2) ascending doses of PUR1900 for up to 14 days. In Part 3 stable, adult asthmatics received a single dose of 20 mg PUR1900 or 200 mg of oral Sporanox (itraconazole oral solution) in a 2-period randomized cross-over design. Itraconazole plasma and sputum concentrations were evaluated. RESULTS: None of the adverse events considered as at least possibly related to study treatment were moderate or severe, and none were classed as serious. The most common was the infrequent occurrence of mild cough. Itraconazole plasma exposure increased with increasing doses of PUR1900. After 14 days, PUR1900 resulted in plasma exposure (area under the concentration-time curve up to 24 h) 106- to 400-fold lower across doses tested (10-35 mg) than steady-state exposure reported for oral Sporanox 200 mg. In asthmatics, PUR1900 geometric mean maximum sputum concentrations were 70-fold higher and geometric mean plasma concentrations were 66-fold lower than with oral Sporanox. CONCLUSION: PUR1900 was safe and well-tolerated under the study conditions. Compared to oral dosing, PUR1900 achieved higher lung and lower plasma exposure. The pharmacokinetic profile of PUR1900 suggests the potential to improve upon the efficacy and safety profile observed with oral itraconazole.

Do non-ruminant wildlife pose a risk of paratuberculosis to domestic livestock and vice versa in Scotland?

Paratuberculosis (Johne's disease) was long considered only a disease of ruminants. Recently non-ruminant wildlife species have been shown to harbor Mycobacterium avium subsp. paratuberculosis, the causative organism of paratuberculosis. We review the known non-ruminant wildlife host range of M. avium subsp. paratuberculosis and consider their role in the epidemiology of paratuberculosis in domestic ruminant livestock. Mycobacterium avium subsp. paratuberculosis has been isolated from lagomorph, canid, mustelid, corvid, and murid species. In agricultural environments domestic ruminants may contact wildlife and/or their excreta when grazing or feeding on farm-stored feed contaminated with wildlife feces, opening up the possibility of inter-species transmission. Of the wildlife species known to harbor M. avium subsp. paratuberculosis in Scotland, the rabbit is likely to pose the greatest risk to grazing livestock. Paratuberculosis in domestic ruminants is a notoriously difficult disease to control; the participation of non-ruminant wildlife in the epidemiology of the disease may partially account for this difficulty.

Using Travel Diary Data to Estimate the Emissions Impacts of Transportation Strategies: The Puget Sound Telecommuting Demonstration Project.

Transportation control measures are often implemented for their environmental benefits, but there is a need to quantify what benefits actually occur. Telecommuting has the potential to reduce the number of daily trips and miles traveled with personal vehicles and, consequently, the overall emissions resulting from vehicle activity. This search studies the emissions impacts of telecommuting for the participants of the Puget Sound Telecommuting Demonstration Project (PSTDP). The California Air Resources Board's emissions models, EMFAC7F and BURDEN7F, are used to estimate the emissions on telecommuting days and non-telecommuting days, based on travel diaries completed by program participants. This study, among the first of its kind, represents the most sophisticated application of emissions models to travel diary data. Analysis of the travel diary data and the emissions model output supports the hypothesis that telecommuting has beneficial transportation and air quality impacts. The most important results are that telecommuting decreases the number of daily trips (by 30%), the vehicle-miles traveled (VMT) (by 63%), and the number of cold starts (by 44%), especially those taking place in early morning. These reductions are shown to have a large effect on daily emissions, with a 50% to 60% decrease in pollutants generated by a telecommuter's personal vehicle use on a telecommuting day. These net savings are almost entirely due to the elimination of commute trips, as non-commute trips increased by 0.33 trips per person-day (9% of the total trips), and the non-commute VMT increased by 2.2 miles. Overall reduc- tions in travel and emissions of this magnitude are observed because the telecommuters in this sample are long-distance commuters, with commutes twice as long as the regional average. However, even as telecommuting adoption moves into the mainstream, its net impacts are still expected to be beneficial- a reduction in VMT and in emissions. It is important to note that when the level of telecommuting is considered (that is, the percentage of work days that employees actually telecommute), the weekly savings are a much smaller proportion of total weekday travel. Also, these findings represent average per-capita reductions; the aggregate (or overall, regionwide) impacts are determined by scaling these reductions by the number of program participants. Thus, the aggregate effectiveness of telecommuting must take into account the number of people likely to participate as telecommuters and how often they telecommute, not just the per-capita, peroccasion impacts.