[CAS NO. 170098-38-1]  Alvimopan dihydrate (LY246736 dihydrate)

In animals, alvimopan antagonizes centrally mediated, morphine-induced analgesia only at relatively high doses, with very high plasma concentrations needed to cross the blood-brain barrier. After intravenous administration, alvimopan is approximately 200-times more potent at blocking peripheral verses central μ-receptors. After oral administration, alvimopan is also highly active. In dogs, intravenous administration of alvimopan provided dose-dependent increases in peak plasma concentrations and plasma area under the concentration-time curve. However, as a result of poor systemic absorption, oral doses up to 100 mg/kg produced low plasma concentrations (mean Cmax =92.9 ng/ml), which resulted in an oral bioavailability of approximately 0.03%. The half-life of alvimopan is estimated to be approximately 10 min after intravenous administration in dogs and rabbits.