Carbamylglutamic acid

190.15

190.15

1308068-626-2

5L0HB4V1EW

DTXSID7046706

C76884

A16AA05|A - Alimentary tract and metabolism

130

-2.4

Solid

1.499g/cm3

157-159 °C

438.1°C at 760 mmHg

218.8ºC

1.544

2-8°C

6.7E-09mmHg at 25°C

NONH for all modes of transport

3

36/37/38

26-36/37

LZ9870000

Xi

P261-P305 + P351 + P338

H302-H315-H319-H335

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 40 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

LD50, oral, mouse: >1000 mg/kg

The urea cycle disorders include at least 8 genetic conditions, one of the more rare causes being NAGS. Because this condition is so rare, carglumic acid was given orphan disease drug status and approval was based on open labelled treatment studies of only 40 patients. In these studies, carglumic acid was not linked to serum enzyme elevations during treatment or to episodes of acute, clinically apparent liver injury or jaundice. Since approval, there have been no published reports of hepatotoxicity attributed to carglumic acid and the product label does not mention liver injury as an adverse event.

For the treatment of acute and chronic hyperammonaemia in patients with N-acetylglutamate synthase (NAGS) deficiency. This enzyme is an important component of the urea cycle to prevent build up of neurotoxic ammonium in the blood.|FDA Label|Ucedane is indicated in treatment of:hyperammonaemia due to N-acetylglutamate synthase primary deficiency;Hyperammonaemia due to isovaleric acidaemia;Hyperammonaemia due to methymalonic acidaemia;Hyperammonaemia due to propionic acidaemia. |Carbaglu is indicated in treatment of:hyperammonaemia due to N-acetylglutamate-synthase primary deficiency;hyperammonaemia due to isovaleric acidaemia;hyperammonaemia due to methymalonic acidaemia;hyperammonaemia due to propionic acidaemia.

Carglumic acid is an orphan drug and a derivative of N-acetylglutamate that activates the first enzyme in the urea cycle that is responsible for removal and detoxification of ammonia, making this drug a valuable agent for therapy of hyperammonemia caused by rare forms of urea cycle defects. Clinical experience with carglumic acid is limited, but it has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.

Urea Cycle Disorder Agents

The median Tmax of Carbaglu was 3 hours (range: 2-4). The daily dose of carglumic acid ranges from 100 to 250 mg/kg and this does are normally adjusted to maintain normal plasma levels of ammonia.

30% bioavailability; Cmax, mean, 100 mg/kg dose = 2.6 μg/mL (range of 1.9 - 4.8) Carglumic acid is not subject to to intracellular degradation.|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).

A proportion of carglumic acid may be metabolized by the intestinal bacterial flora. The likely end product of carglumic acid metabolism is carbon dioxide, eliminated through the lungs.

Median values for the terminal half-life was 5.6 hours (range 4.3-9.5).

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 found in the mitochondria and 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 but it does not help to regulate the urea cycle.

carbamylglutamate

Human drugs -> Ucedane -> EMA Drug Category|Other alimentary tract and metabolism products -> Human pharmacotherapeutic group|Human drugs -> Carbaglu -> EMA Drug Category|Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients