Although many processes are well understood at a point or for a small area, others are poorly understood at all scales, and process interactions under normal or extreme climatic conditions may be unknown. Basin models typically combine land-surface process components (to estimate how much rainfall or snowmelt reaches a channel) with a series of reach models. For example, a basin model can calculate the runoff hydrograph that might result from a 100-year storm, although the recurrence interval of a storm is rarely equal to that of the associated flood. Basin models are commonly used in flood forecasting and warning, as well as in analysis of the effects of land use change and climate change. Flood forecasting
Anticipating floods before they occur allows for precautions to be taken and people to be warned so that they can be prepared in advance for flooding conditions. For example, farmers can remove animals from low-lying areas and utility services can put in place emergency provisions to re-route services if needed. Emergency services can also make provisions to have enough resources available ahead of time to respond to emergencies as they occur. People can evacuate areas to be flooded. In order to make the most accurate flood forecasts for waterways, it is best to have a long time-series of historical data that relates stream flows to measured past rainfall events.
As the area under the curve is not significantly different with or without a meal, the drug can be taken independently of food. Once in the bloodstream, 93 to 94% of the substance is bound to plasma proteins, mainly to albumin.Naldemedine is mainly metabolized by the enzyme CYP3A4 to nor-naldemedine (which makes up about 9–13% of the circulating substance), and to a much lesser extent by UGT1A3 to naldemedine 3-glucuronide. Minor metabolites are the 6-glucuronide, the 7-(R/S)-hydroxy-derivates, and two products formed by enterobacteria through cleaving the oxadiazole ring: naldemedine carboxylic acid and benzamidine. Nor-naldemedine, the glucuronides, and the carboxylic acid are opioid receptor antagonists, but less potent than the original substance. Naldemedine and its metabolites are excreted via urine and faeces. The part of the molecule "left" of the cleavage line (the sum of original substance, nor-naldemedine, glucuronides, hydroxy-derivative, and carboxylic acid) is found to 20.4% in the urine and to 64.3% in the faeces, while the part "right" to the line (the sum of original substance, nor-naldemedine, glucuronides, hydroxy-derivative, and benzamidine) is found to 57.3% in the urine and to 34.8% in the faeces. This indicates that benzamidine is predominantly excreted in the urine and the carboxylic acid is predominantly excreted in the faeces. The terminal half-life is about 11 hours. Chemistry
Naldemedine is used in form of the tosylate, a white to light tan powder. It is not hygroscopic and has a high water solubility at a physiologic pH.