Sacubitrilat (LBQ657) is a single diastereomer with specific stereocenters. Sacubitrilat is bound to the active site of NEP by an intricate network of interactions that involves all functional groups of the compound giving rise to the high inhibitory potency of 5 nM.
Pharmacokinetics of Sacubitril, Sacubitrilat (LBQ657), and valsartan following the administration of single oral doses of LCZ696 400 or 1200 mg under fasting condition are summarized. The mean plasma concentrations of Sacubitril increases rapidly with a median T max of 0.52 h for the 400 mg dose and 1.05 h for the 1200 mg dose, followed by Sacubitrilat, with the corresponding T max values of 2.07 and 3.05 h, respectively. The median T max for valsartan is 2.07 h for both the LCZ696 400 mg and 1200 mg doses. The C max of Sacubitrilat shows a dose proportional increase, while the C max of Sacubitril and Valsartan shows less than proportional increases between the doses. The arithmetic mean AUC 0-24 h and AUC last for Sacubitril and Sacubitrilat increases approximately dose proportionally, but shows less than dose proportional increase for Valsartan.