| Item |
Information |
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Drug Groups
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approved |
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Description
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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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Elpeleg O, Shaag A, Ben-Shalom E, Schmid T, Bachmann C: N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845-9.
[Pubmed]
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Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M: Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct;145(4):552-4.
[Pubmed]
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Summary of the European Public Assessment Report (EPAR) from European Medicines Agency. Last updated on 21/09/2009.
[Carbaglu]
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Thompson CA: Carglumic acid approved to treat genetic hyperammonemia. Am J Health Syst Pharm. 2010 May 1;67(9):690.
[Pubmed]
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| External Links |
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