Drug Groups

approved

Description

Carglumic acid is an orphan drug used for the treatment of hyperammonaemia in patients with N-acetylglutamate synthase deficiency. This rare genetic disorder results in elevated blood levels of ammonia, which can eventually cross the blood–brain barrier and cause neurologic problems, cerebral edema, coma, and death. Carglumic acid was approved by the U.S. Food and Drug Administration (FDA) on 18 March 2010.

Indication

For the treatment of hyperammonaemia in patients with N-acetylglutamate synthase (NAGS) deficiency.

Pharmacology

The median Tmax of Carbaglu was 3 hours (range: 2-4). The initial daily dose ranges from 100 to 250 mg/kg, adjusted thereafter to maintain normal plasma levels of ammonia.

Biotransformation

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.

Absorption

30% bioavailability

Half Life

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

Elimination

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.

Distribution

The apparent volume of distribution was 2657 L (range: 1616-5797).

Clearance

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).

References

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