For the treatment of hyperammonaemia in patients with N-acetylglutamate synthase (NAGS) deficiency.
Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG), which is an essential allosteric activator of the liver enzyme carbamoyl phosphate synthetase 1 (CPS1). CPS1 is the first enzyme of the urea cycle, which converts ammonia into urea. Carglumic acid acts as a replacement for NAG in NAGS deficiency patients by activating CPS1.
Median values for the terminal half-life was 5.6 hours (range 4.3-9.5).
Following administration of a single radiolabeled oral dose of 100 mg/kg of body weight, 9% of the dose was excreted unchanged in the urine and up to 60% of the dose was excreted unchanged in the feces.
The apparent volume of distribution was 2657 L (range: 1616-5797).
The apparent total clearance was 5.7 L/min (range 3.0-9.7), the renal clearance was 290 mL/min (range 204-445), and the 24-hour urinary excretion was 4.5 % of the dose (range 3.5-7.5).