Metformin is distributed to (and appears to accumulate in) red blood cells, with a much longer elimination half-life: 17.6 hours (reported as ranging from 18.5 to 31.5 hours in a single-dose study of nondiabetics).Some evidence indicates that liver concentrations of metformin in humans may be two to three times higher than plasma concentrations, due to portal vein absorption and first-pass uptake by the liver in oral administration. Chemistry
Metformin hydrochloride (1,1-dimethylbiguanide hydrochloride) is freely soluble in water, slightly soluble in ethanol, but almost insoluble in acetone, ether, or chloroform. The pKa of metformin is 12.4. The usual synthesis of metformin, originally described in 1922, involves the one-pot reaction of dimethylamine hydrochloride and 2-cyanoguanidine over heat. According to the procedure described in the 1975 Aron patent, and the Pharmaceutical Manufacturing Encyclopedia, equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and an equimolar amount of hydrogen chloride is slowly added. The mixture begins to boil on its own, and after cooling, metformin hydrochloride precipitates with a 96% yield. Derivatives
A new derivative HL156A, also known as IM156, is potential new drug for medical use. History
The biguanide class of antidiabetic medications, which also includes the withdrawn agents phenformin and buformin, originates from the French lilac or goats rue (Galega officinalis), a plant used in folk medicine for several centuries.
A choriovitelline placenta is a placenta formed by the yolk sac and chorion. In a choriovitelline placenta, the yolk sac fuses with the chorion and, subsequently, wrinkles develop that hold the embryo to the uterine wall, thus forming the choriovitelline placenta. The chorionic blood vessels are connected with the vitelline blood vessel of the yolk sac. It is a primitive type of placenta found in all marsupials. (However, bandicoots also have a chorioallantoic placenta.) A choriovitelline placenta also forms early in the development of some placental mammals before the chorioallantoic placenta forms and the choriovitelline placenta is resorbed. == References ==