Glycerol phenylbutyrate in patients with cirrhosis and episodic hepatic encephalopathy: A pilot study of safety and effect on venous ammonia concentration

Clinical Pharmacology in Drug Development

Volumn 2, Issue 3, 2013, Pages 278-284

  Ghabril, Marwan ^a   Zupanets, Igor A ^b   Vierling, John ^c   Mantry, Parvez ^d   Rockey, Don ^e   Wolf, David ^f   O'Shea, Robert ^g   Dickinson, Klara ^h   Gillaspy, Heather ^h   Norris, Catherine ^h   Coakley, Dion F ^h   Mokhtarani, Masoud ^h   Scharschmidt, Bruce F ^h  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL UNIVERSITY OF PHARMACY   (Ukraine)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

^d METHODIST DALLAS MEDICAL CENTER   (United States)

^e UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^f NEW YORK MEDICAL COLLEGE   (United States)

^g LERNER RESEARCH INSTITUTE   (United States)

^h Hyperion Therapeutics Inc   (United States)

Author keywords

Ammonia; Cirrhosis; Hepatic encephalopathy; Phenylacetylglutamine; Phenylbutyrate

Indexed keywords

AMMONIA; GLYCEROL PHENYLBUTYRATE;

ADULT; AMMONIA BLOOD LEVEL; ANEMIA; AREA UNDER THE CURVE; ARTICLE; CHILD PUGH SCORE; CLINICAL ARTICLE; CONNECTIVE TISSUE DISEASE; DIABETES MELLITUS; DIARRHEA; DISEASE CLASSIFICATION; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ESOPHAGUS VARICES BLEEDING; FEMALE; GASTROINTESTINAL DISEASE; HEMATOLOGIC DISEASE; HEPATIC ENCEPHALOPATHY; HUMAN; HYPOGLYCEMIA; HYPOKALEMIA; HYPONATREMIA; INFECTION; INFESTATION; INJURY; INTOXICATION; KIDNEY DISEASE; KIDNEY FAILURE; LIVER CIRRHOSIS; LIVER FAILURE; LYMPHATIC SYSTEM DISEASE; MALE; MAXIMUM PLASMA CONCENTRATION; MENTAL DISEASE; METABOLIC DISORDER; MUSCULOSKELETAL DISEASE; NAUSEA; NEUROLOGIC DISEASE; NUTRITIONAL DISORDER; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; PILOT STUDY; PLASMA CONCENTRATION-TIME CURVE; POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME; PRIORITY JOURNAL; SIDE EFFECT; SKIN DISEASE; THROMBOCYTOPENIA; TREATMENT OUTCOME; UPPER ABDOMINAL PAIN; URINARY TRACT DISEASE; URINARY TRACT INFECTION;

EID: 84892488882     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1002/cpdd.18     Document Type: Article

References (14)

1. Bass NM. Emerging treatment options for the management of hepatic encephalopathy. Semin Liver Dis. 2007; 27(Suppl 2):18-25.
2. Ferenci P. Treatment options for hepatic encephalopathy: a review. Semin Liver Dis. 2007; 27(Suppl 2):10-17.
3. Mullen KD, Ferenci P, Bass NM, et al. An algorithm for the management of hepatic encephalopathy. Semin Liver Dis. 2007; 27(Suppl 2):32-48.
4. Rudman D, DiFulco TJ, Galambos JT, et al. Maximal rates of excretion and synthesis of urea in normal and cirrhotic patients. J Clin Invest. 1973; 52:2241-2249.
5. Ong JP, Aggarwal A, Krieger D, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med. 2003; 114:188-193.
6. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010; 362:1071-1081.
7. Sanyal A, Bass N, Poordad F, et al. Rifaximin decreases venous ammonia concentrations and time-weighted average ammonia concentrations correlate with overt hepatic encephalopathy (HE) as assessed by Conn score in a 6-month study. J Hepatol. 2010; 52:S84.
8. Lee B, Rhead W, Diaz GA, et al. Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control. Mol Genet Metab. 2010; 100:221-228.
9. McGuire BM, Zupanets I, Lowe ME, et al. Pharmacology and safety of a novel ammonia lowering agents in healthy adults and adults with cirrhosis. Hepatology. 2010; 51:2077-2085.
10. Lichter-Konecki U, Diaz GA, Merritt JL II, et al. Ammonia (NH3) control in children with urea cycle disorders (UCDs); comparison of sodium phenylbutyrate and glycerol phenylbutyrate mol. Genet Metab. 2011; 103:323-329.
11. Diaz GA, Krivitsky LS, Mokhtarani M, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. [serial online]. September 7, 2012. doi: 10.1002/hep.26058 [epub ahead of print].
12. Thibault A, Samid D, Cooper MR, et al. A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer. Cancer Res. 1994; 54:1690-1694.
13. Thibault A, Cooper MR, Figg WD, et al. Phase I study of phenylacetate administered twice daily to patients with cancer. Cancer. 1995; 75:2932-2938.
14. Rockey D, Vierling J, Mantry P, et al. Randomized, controlled, double-blind study of glycerol phenylbutyrate in patients with cirrhosis and episodic hepatic encephalopathy. Hepatology. 2012; 56:248A.