title: Ornithine phenylacetate revisited.
abstract: In patients with liver failure hyperammonemia is associated with the development of hepatic encephalopathy (HE) and immune impairment. Treatment of hyperammonemia is an unmet clinical need. Ornithine phenylacetate (OP) is a novel drug that is targeted at reducing ammonia concentration in patients with liver disease and therefore a potential treatment for HE. This review describes the mechanism of action of OP and its effect on plasma ammonia levels, brain function and inflammation of OP in both acute and chronic liver failure. Ammonia levels could shown to be reduced for up to 24 h in animal models until 120 h in patients with repeated dosing of the drug. Reduction of plasma ammonia levels is due to the stimulation of ammonia removal in the form of glutamine (through glutamine synthetase), the direct excretion of ammonia in the form phenylacetylglutamine and to a normalisation of glutaminase activity in the gut. Administration of OP is associated with a reduction of brain oedema in rats with chronic bile duct ligation and diminution of intracranial hypertension in a pig model of ALF. Studies to date have indicated that it is safe in humans and trials in overt HE are underway to establish OP as a treatment for this major complication of liver disease.
authors: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, Pond Street, London NW3 2PF, UK. m.cobos@ucl.ac.uk
authors: Maria
authors: M
authors: Jover-Cobos
authors: Lorette
authors: L
authors: Noiret
authors: Yalda
authors: Y
authors: Sharifi
authors: Rajiv
authors: R
authors: Jalan
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism*; D017093:Liver Failure / Q000188:drug therapy / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats
chemical_list: C572232:ornithine phenylacetate; D009952:Ornithine