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.
The mother has approximately 10 minutes to get to a doctor before there is any harm done to the fetus. Monoamniotic twins – These twins share the same placenta and the same amniotic sac and therefore can interfere with each others umbilical cords. When entanglement of the cords is detected, it is highly recommended to deliver the fetuses as early as 31 weeks. Umbilical cord length - A short umbilical cord (<30 cm) can affect the fetus in that fetal movements can cause cord compression, constriction, and rupture. A long umbilical cord (>72 cm) can affect the fetus depending on the way the fetus interacts with the cord. Some fetuses grasp the umbilical cord but it is yet unknown as to whether a fetus is strong enough to compress and stop blood flow through the cord. Also, an active fetus, one that frequently repositions itself in the uterus can accidentally entangle itself with the cord. A hyperactive fetus should be evaluated with ultrasound to rule out cord entanglement. Cord entanglement - The umbilical cord can wrap around an extremity, the body or the neck of the fetus. When the cord is wrapped around the neck of the fetus, it is called a nuchal cord. These entanglements can cause constriction of blood flow to the fetus. These entanglements can be visualized with ultrasound. Torsion – This term refers to the twisting of the umbilical around itself.