Fexinidazole – A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness

This article describes the preclinical profile of fexinidazole, a new drug candidate with the potential to become a novel, oral, safe and effective short-course treatment for curing both stage 1 and 2 human African trypanosomiasis and replace the old and highly problematic treatment modalities available today. Fexinidazole is orally available and rapidly metabolized in two metabolites having equivalent biological activity to the parent and contributing significantly to the in vivo efficacy in animal models of both stage 1 and 2 HAT. Animal toxicology studies indicate that fexinidazole has an excellent safety profile, with no particular issues identified. Fexinidazole is a 5-nitroimidazole and, whilst it is Ames-positive, it is devoid of any genetic toxicity in mammalian cells and therefore does not pose a genotoxic risk for use in man. Fexinidazole, which was rediscovered through a process of compound mining, is the first new drug candidate for stage 2 HAT having entered clinical trials in thirty years, and has the potential to revolutionize therapy of this fatal disease at a cost that is acceptable in the endemic regions

Patient satisfaction in pediatric outpatient settings from the parents’ perspective - The Child ZAP: A psychometrically validated standardized questionnaire

<p>Abstract</p> <p>Background</p> <p>Patient surveys constitute a valuable source of information in patient-focused health care. The objective of this study was to develop and validate a standardized, patient centered, quantitative instrument to assess parent satisfaction in ambulatory pediatric care to be used in quality management and benchmarking activities, the Child-ZAP.</p> <p>Methods</p> <p>A preliminary version of the survey (38 items) was conducted in n = 19 pediatric practices. After psychometric testing a modified Child-ZAP was tested in a second survey (n = 20 new pediatric practices). Data from n = 979 patients were available for analysis.</p> <p>Results</p> <p>The final version of the Child-ZAP contains eight dimensions, three "Child-Scales" and five "Parent-Scales". Confirmatory factor analysis confirms the three hypothesized child dimensions as well as the five parent dimensions. The factorial structure is confirmed in subgroups of younger and older children.</p> <p>Conclusions</p> <p>With satisfactory to good results for validity and reliability testing, the final Child-ZAP is applicable in pediatric ambulatory care for children of all age groups.</p

Structure-function of cytochromes P450 and flavin-containing monooxygenases - Implications for drug metabolism

This article is a report on a symposium held at Experimental Biology '98 in San Francisco, California. Recent developments in site-directed mutagenesis, computer-modeling, and mechanistic analysis of cytochromes P450 and flavin-containing monooxygenases are described. A unifying theme is the elaboration of general approaches for understanding and predicting the function of individual forms of these enzymes. A related goal is the production of soluble forms of mammalian cytochromes P450 for X-ray crystallography