GLYCEROL PHENYLBUTYRATE IS INDICATED FOR USE AS A NITROGEN-BINDING AGENT FOR CHRONIC MANAGEMENT OF ADULT AND PEDIATRIC PATIENTS =>2 YEARS OF AGE WITH UREA CYCLE DISORDERS (UCDS) WHO CANNOT BE MANAGED BY DIETARY PROTEIN RESTRICTION AND/OR AMINO ACID SUPPLEMENTATION ALONE. GLYCEROL PHENYLBUTYRATE MUST BE USED WITH DIETARY PROTEIN RESTRICTION AND, IN SOME CASES, DIETARY SUPPLEMENTS (E.G., ESSENTIAL AMINO ACIDS, ARGININE, CITRULLINE, PROTEIN-FREE CALORIE SUPPLEMENTS).
UCDS ARE INHERITED DEFICIENCIES OF ENZYMES OR TRANSPORTERS NECESSARY FOR THE SYNTHESIS OF UREA FROM AMMONIA (NH3, NH4 +). ABSENCE OF THESE ENZYMES OR TRANSPORTERS RESULTS IN THE ACCUMULATION OF TOXIC LEVELS OF AMMONIA IN THE BLOOD AND BRAIN OF AFFECTED PATIENTS. GLYCEROL PHENYLBUTYRATE IS A TRIGLYCERIDE CONTAINING 3 MOLECULES OF PHENYLBUTYRATE (PBA). PAA, THE MAJOR METABOLITE OF PBA, IS THE ACTIVE MOIETY OF RAVICTI. PAA CONJUGATES WITH GLUTAMINE (WHICH CONTAINS 2 MOLECULES OF NITROGEN) VIA ACETYLATION IN THE LIVER AND KIDNEYS TO FORM PAGN, WHICH IS EXCRETED BY THE KIDNEYS (FIGURE 1). ON A MOLAR BASIS, PAGN, LIKE UREA, CONTAINS 2 MOLES OF NITROGEN AND PROVIDES AN ALTERNATE VEHICLE FOR WASTE NITROGEN EXCRETION