Delving into the Latest Updates on Ornithine Phenylacetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

L-OP, L-Ornithine phenylacetate, OP

+ [9]

Target

NF-κB x NOS2

Mechanism

NF-κB inhibitors(Nuclear factor NF-kappa-B complex inhibitors), NOS2 modulators(Nitric oxide synthase, inducible modulators)

Therapeutic Areas

Nervous System DiseasesDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Chemical and Drug Induced Liver InjuryFibrosisHepatic Encephalopathy+ [3]

Originator Organization

University College London

Active Organization-

Inactive Organization

OCERA Therapeutics LLC

Mallinckrodt Plc

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (EU)

Structure

Molecular FormulaC13H20N2O4

InChIKeyLRSYFEZBIMVWRY-VWMHFEHESA-N

CAS Registry952154-79-9

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of MNK6105 (an Intravenous Formulation of L-Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Hyperammonemia Associated With an Episode of Hepatic Encephalopathy

This study is for patients with cirrhosis and hepatic encephalopathy who are in the hospital. This means they have a high ammonia level which is affecting their brain function.
All patients will receive the standard of (regular) care. Each will have an equal chance (like flipping a coin) of receiving the experimental drug or placebo along with the standard care.
Each patient will have tests during the first 24 hours, receive treatment for up to 5 days, and have 30 days of follow-up.

Start Date01 Nov 2021

Sponsor / Collaborator

Mallinckrodt Plc

NCT03712280 / CompletedPhase 2

A Randomized, Open-Label, Phase 2a Comparator Study to Assess the Pharmacodynamics, Safety and Pharmacokinetics of Oral Administration MNK6106 (L-Ornithine Phenylacetate) Versus Rifaximin in Subjects With Hepatic Cirrhosis and a History of Prior Episodes of Hepatic Encephalopathy

The main reason for this study is to see how the study drug interacts with the body.
It will compare different doses of the study drug with a drug already in use.
Participants will be adults with liver disease that has affected the brain in the past.

Start Date01 Dec 2018

Sponsor / Collaborator

Mallinckrodt Plc

NCT03846843 / CompletedPhase 1

An Open-Label, Two-Part, Phase 1/2a, Crossover Study to Determine the Absolute Bioavailability and Pharmacokinetics of Oral Immediate-Release Doses of OCR-002 in Subjects With Varying Degrees of Cirrhosis

This is an open-label Phase 1, 2-part, crossover study in approximately 33 adult subjects (12 subjects in Part 1 and 21 subjects in Part 2), with varying degrees of cirrhosis with analysis of pharmacokinetic (PK) data after Part 1 to guide dose regimen selection and PK sampling time points for OCR-002 in Part 2.

Start Date15 Aug 2016

Sponsor / Collaborator

OCERA Therapeutics LLC

100 Clinical Results associated with Ornithine Phenylacetate

Login to view more data

100 Translational Medicine associated with Ornithine Phenylacetate

Login to view more data

100 Patents (Medical) associated with Ornithine Phenylacetate

Login to view more data

1,614

Literatures (Medical) associated with Ornithine Phenylacetate

01 Mar 2024·Environmental pollution (Barking, Essex : 1987)

Levels, distribution, sources and human exposure pathways of alkylphenol and alkylphenol ethoxylates in indoor dust in Turkiye

Article

Author: Güllü, Gülen ; Babaei, Parisa ; Nikravan Madan, Efsun ; Gül, Hatice Kübra ; Kurt Karakuş, Perihan Binnur ; Gören, İsmail Ethem ; Dağlıoğlu, Nebile

Environmental phenolic chemicals, due to their widespread occurrence and potent estrogenic properties, pose a risk to human exposure. The phenolic organic contaminants alkylphenols (APs) and alkylphenol polyethoxylates (APEs) are used in various household applications, and they may enter to the environment during production and use, potentially appearing in indoor dust. However, little is known about the levels of environmental phenolics in indoor environments. In this study, five of these compounds namely octylphenol (OP), 4-Octylphenol Monoethoxylate (4-OPME), 4-tert-octylphenol (4-t-OP), 4-n-nonylphenol (4-n-NP) and nonylphenol diethoxylate (di-NPE) were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in household dust samples (n = 148) collected from Ankara, the capital of Turkiye. OP and 4-OPME was not present in any of the analyzed samples. The median concentrations of the 148 settling dust samples were 35, 520, and 1910 ng g^-1 dust for 4-t-OP, 4-n-NP, and di-NPE, respectively. An assessment of the human (children and adults) exposure pathway to APs and APEs, which are recognized as endocrine-disrupting chemicals found in residential dust, revealed that it was approximately 3 times higher for children than for adults at both moderate and heavy exposure levels. The association between chemical exposure, house characteristics, and family lifestyle was investigated using a multivariate logistic regression model. According to the results of this model, while the high concentrations measured for 4-t-OP were not found to be associated with any of the household parameters, high levels of 4-n-NP and di-NPE were associated with the frequency of house cleaning, repairs made during the previous year, residential type, the number of occupants, flooring materials, and the purchase of new household items within the past year. This study provides a basis for prioritizing toxicology and exposure studies for EDCs and mixtures and may offer new tools for exposure assessment in health studies.

03 Mar 2024·Drug development and industrial pharmacy

Physicochemical interaction of rifampicin and ritonavir-lopinavir solid dispersion: an in-vitro and ex-vivo investigation

Article

Author: Bheemisetty, Brahmam ; Nair, Athira R ; Bhat, Krishnamurthy ; Yarlagadda, Dani Lakshman ; Vullendula, Sai Krishna Anand ; Dengale, Swapnil J

OBJECTIVE:

To investigate the in-situ physicochemical interaction of Rifampicin and Ritonavir - Lopinavir Solid dispersion administered for the treatment of comorbid conditions i.e. Tuberculosis and HIV/AIDS.

METHODS:

pH-shift dissolution of Rifampicin (RIF) in presence of Ritonavir-Lopinavir solid dispersion (RL-SD) was carried out in USP phosphate buffer 6.8 and FaSSIF. Equilibrium and amorphous solubility were determined for the drugs. Pure drugs, their physical mixtures, and pH-shifted co-precipitated samples were characterized using DSC, PXRD, and FTIR. Fluorescence spectroscopy was used to investigate drug-rich and drug-lean phases. In-vitro and ex-vivo flux studies were also carried out.

RESULTS:

The results showed significant differences in the solubility and dissolution profiles of RTV and LOP in the presence of RIF, while RIF profile remained unchanged. Amorphicity, intermolecular interaction and aggregate formation in pH-shifted samples were revealed in DSC, XRD and FTIR analysis. Fluorescence spectroscopy confirmed the formation of drug-rich phase upon pH-shift. In-vitro and ex-vivo flux studies revealed significant reduction in the flux of all the drugs when studied in presence of second drug.

CONCLUSION:

RIF, RTV and LOP in presence of each other on pH-shift, results in co-precipitation in the amorphous form (miscible) which leads to reduction in the highest attainable degree of supersaturation. This reduction corresponds to the mole fraction of the RIF, RTV and LOP within the studied system. These findings suggest that the concomitant administration of these drugs may lead to physicochemical interactions and possible ineffective therapy.

01 Feb 2024·The Journal of pharmacology and experimental therapeutics

Chronic Epilepsy and Mossy Fiber Sprouting Following Organophosphate-Induced Status Epilepticus in Rats

Article

Author: Deshpande, Laxmikant S ; DeLorenzo, Robert J ; Blair, Robert E ; Pinchbeck, Lauren R ; Hawkins, Elisa

Organophosphate (OP) compounds are highly toxic and include pesticides and chemical warfare nerve agents. OP exposure inhibits the acetylcholinesterase enzyme, causing cholinergic overstimulation that can evolve into status epilepticus (SE) and produce lethality. Furthermore, OP-induced SE survival is associated with mood and memory dysfunction and spontaneous recurrent seizures (SRS). In male Sprague-Dawley rats, we assessed hippocampal pathology and chronic SRS following SE induced by administration of OP agents paraoxon (2 mg/kg, s.c.), diisopropyl fluorophosphate (4 mg/kg, s.c.), or O-isopropyl methylphosphonofluoridate (GB; sarin) (2 mg/kg, s.c.), immediately followed by atropine and 2-PAM. At 1-hour post-OP-induced SE onset, midazolam was administered to control SE. Approximately 6 months after OP-induced SE, SRS were evaluated using video and electroencephalography monitoring. Histopathology was conducted using hematoxylin and eosin (H&E), while silver sulfide (Timm) staining was used to assess mossy fiber sprouting (MFS). Across all the OP agents, over 60% of rats that survived OP-induced SE developed chronic SRS. H&E staining revealed a significant hippocampal neuronal loss, while Timm staining revealed extensive MFS within the inner molecular region of the dentate gyrus. This study demonstrates that OP-induced SE is associated with hippocampal neuronal loss, extensive MFS, and the development of SRS, all hallmarks of chronic epilepsy. SIGNIFICANCE STATEMENT: Models of organophosphate (OP)-induced SE offer a unique resource to identify molecular mechanisms contributing to neuropathology and the development of chronic OP morbidities. These models could allow the screening of targeted therapeutics for efficacious treatment strategies for OP toxicities.

100 Deals associated with Ornithine Phenylacetate

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D09942	-	-	-

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hepatic Encephalopathy	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Hyperammonemia	Phase 3	-	Mallinckrodt Plc	01 Nov 2021
Liver Cirrhosis	Phase 2	US	Mallinckrodt Plc	01 Dec 2018
Liver Cirrhosis	Phase 2	PR	Mallinckrodt Plc	01 Dec 2018
Chemical and Drug Induced Liver Injury	Phase 2	US	OCERA Therapeutics LLC	01 Jun 2012
Liver Failure, Acute	Phase 2	US	OCERA Therapeutics LLC	01 Jun 2012

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01966419 (STOP-HE, Pubmed \| Clin Gastroenterol Hepatol) Manual	Phase 2	Hepatic Encephalopathy	226	Ornithine Phenylacetate	erfumgglvh(vbixltynmj) = pzjayzbxss vccflftnjs (frkgvfgkww, 34 - 69) View more	Negative	01 Dec 2021
				Placebo	erfumgglvh(vbixltynmj) = gokcxikkse vccflftnjs (frkgvfgkww, 53 - 98) View more
NCT01966419 (STOP-HE, CTgov)	Phase 2	Hepatic Encephalopathy \| Fibrosis \| Hyperammonemia	231	placebo intravenous infusion (Placebo)	aygvrpvoqd(ahbthvsjre) = jqtymfpgvk npujeseryt (tkycztevou, yodcoookzc - liumjmqsce) View more	-	16 Sep 2021
				ornithine phenylacetate (Ornithine Phenylacetate)	aygvrpvoqd(ahbthvsjre) = ursbjxozti npujeseryt (tkycztevou, jldqvmbfsu - vwnmnqqyez) View more
NCT03712280 (CTgov)	Phase 2	Hepatic Encephalopathy \| Liver Cirrhosis	50	MNK6106 (Group A: MNK6106 2 Grams (Tid))	bmuoykbqnj(nppbdrzsex) = lwqmecqhfa kqufpdbzqa (tfvqdmkayz, nviczdzngc - kytitwdqoq) View more	-	20 Jul 2021
				MNK6106 (Group B: MNK6106 4 Grams (Bid))	bmuoykbqnj(nppbdrzsex) = mnnyehdszy kqufpdbzqa (tfvqdmkayz, xpyqlrbrui - kdxzgnggfo) View more