A Novel Faster-Acting, Dry Powder-Based, Naloxone Intranasal Formulation for Opioid Overdose.

OBJECTIVE: To examine the pharmacokinetics and safety of FMXIN001, a new intranasal powder-based naloxone formulation, in comparison to Narcan® nasal liquid spray. METHODS: FMXIN001, was developed by blending drug microspheres with larger lactose monohydrate particles, that serve as diluent and carrier, as well as a disaggregating agent. Scanning electron microscopy and X-ray were used to characterize the formulation and in vitro deposition was investigated using a nasal cast. We compared the pharmacokinetics and safety of FMXIN001 versus Narcan® in two clinical trials: a pilot study with 14 healthy adults and a pivotal trial in 42 healthy adults (NCT04713709). The studies were open-label, single-dose, randomized, two-period, two-treatment, two-sequence crossover studies to assess the pharmacokinetics and safety of FMXIN001 versus Narcan® nasal spray. RESULTS: FMXIN001 comprises naloxone microspheres (5-30 µM) and lactose particles (40-240 µM). Upon in vitro testing, naloxone deposits mainly to the middle turbinates region and the upper part of the nasal cavity of a nasal cast. In human subjects, FMXIN001 produced significantly higher exposure at the initial time points of 4, 10, and 30 min, post-administration, compared to Narcan®. Both treatments were safe and well tolerated. FMXIN001, powder-based spray, results in similar overall exposure to Narcan®, but with more rapid absorption in the first 30 min. CONCLUSIONS: FMXIN001 is expected to have a shorter onset of action for a more effective therapeutic intervention to manage opioid overdose. Rapid administration of naloxone in cases of opioid overdose is imperative, given the alarming increase in mortality rates.

Assessment of frequency of diarrhoea in relation to drinking water among residents of Nurpur Shahan, Pakistan.

OBJECTIVES: To determine the source of drinking water and to assess its relationship with the frequency of diarrhoea among households of Nurpur Shahan. METHODS: A cross-sectional descriptive study was carried out in January 2010 with a preformed questionnaire. Systematic random sampling was used to collect data. Participants' consent was obtained and confidentiality was maintained during the survey and during analysis. Households were evaluated for the frequency of diarrhoea in relation to their water source, its purification, and availability of sanitation facilities. All collected data was analyzed using SPSS 10.0. RESULTS: Of the 107 households surveyed, 2.8% used wells, 63% used tap water and 32.7% used hand pumps, whereas only 0.9% consumed store-bought water as their major source of drinking water. The difference in the frequency of diarrhoea between those households who purified their water and those that did not was just 1%. The relationship between the source of drinking water and the frequency of diarrhoea was not statistically significant (p = 0.319). Surprisingly households with no disposal facilities only had a 20% frequency of diarrhoea; this was found to be statistically significant (p = 0.023). CONCLUSIONS: This study contradicts the general conception that water supply is responsible for diarrhoea in the locality of Nurpur Shahan; it was found that the statistical difference between diarrhoea resulting from purified and non purified water was very small (p-value=0.587). Rather, improper sanitation and poor personal hygiene seem largely responsible for diarrhoea in this rural Islamabad community.