Sodium Phenylbutyrate

12/06/2023

4-SODIUM PHENYL BUTYRIC ACID HAS BOTH EFFICACY AND COUNTER-INDICATIVE EFFECTS IN THE TREATMENT OF COL4A1 DISEASE

Abstract

Mutations in the collagen genes COL4A1 and COL4A2 cause Mendelian eye, kidney and cerebrovascular disease including intracerebral haemorrhage (ICH), and common collagen IV variants are a risk factor for sporadic ICH. COL4A1 and COL4A2 mutations cause endoplasmic reticulum (ER) stress and basement membrane (BM) defects, and recent data suggest an association of ER stress with ICH due to a COL4A2 mutation. However, the potential of ER stress as a therapeutic target for the multi-systemic COL4A1 pathologies remains unclear. We performed a preventative oral treatment of Col4a1 mutant mice with the chemical chaperone phenyl butyric acid (PBA), which reduced adult ICH. Importantly, treatment of adult mice with the established disease also reduced ICH. However, PBA treatment did not alter eye and kidney defects, establishing tissue-specific outcomes of targeting Col4a1-derived ER stress, and therefore this treatment may not be applicable for patients with eye and renal disease. While PBA treatment reduced ER stress and increased collagen IV incorporation into BMs, the persistence of defects in BM structure and reduced ability of the BM to withstand mechanical stress indicate that PBA may be counter-indicative for pathologies caused by matrix defects. These data establish that treatment for COL4A1 disease requires a multipronged treatment approach that restores both ER homeostasis and matrix defects. Alleviating ER stress is a valid therapeutic target for preventing and treating established adult ICH, but collagen IV patients will require stratification based on their clinical presentation and mechanism of their mutations.

https://academic.oup.com/hmg/article/28/4/628/5142417

Abstract. Mutations in the collagen genes COL4A1 and COL4A2 cause Mendelian eye, kidney and cerebrovascular disease including intracerebral haemorrhage (ICH), a

10/02/2023

TOPICAL OCULAR SODIUM 4-PHENYLBUTYRATE RESCUES GLAUCOMA IN A MYOCILIN MOUSE MODEL OF PRIMARY OPEN-ANGLE GLAUCOMA

Abstract
Purpose.: Mutations in the myocilin gene (MYOC) are the most common known genetic cause of primary open-angle glaucoma (POAG). The purpose of this study was to determine whether topical ocular sodium 4-phenylbutyrate (PBA) treatment rescues glaucoma phenotypes in a mouse model of myocilin-associated glaucoma (Tg-MYOCY437H mice).

Methods.: Tg-MYOCY437H mice were treated with PBA eye drops (n = 10) or sterile PBS (n = 8) twice daily for 5 months. Long-term safety and effectiveness of topical PBA (0.2%) on glaucoma phenotypes were examined by measuring intraocular pressure (IOP) and pattern ERG (PERG), performing slit lamp evaluation of the anterior chamber, analyzing histologic sections of the anterior segment, and comparing myocilin levels in the aqueous humor and trabecular meshwork of Tg-MYOCY437H mice.

Results.: Tg-MYOCY437H mice developed elevated IOP at 3 months of age when compared with wild-type (WT) littermates (n = 24; P < 0.0001). Topical PBA did not alter IOP in WT mice. However, it significantly reduced elevated IOP in Tg-MYOCY437H mice to the level of WT mice. Topical PBA-treated Tg-MYOCY437H mice also preserved PERG amplitudes compared with vehicle-treated Tg-MYOCY437H mice. No structural abnormalities were observed in the anterior chamber of PBA-treated WT and Tg-MYOCY437H mice. Analysis of the myocilin in the aqueous humor and TM revealed that PBA significantly improved the secretion of myocilin and reduced myocilin accumulation as well as endoplasmic reticulum (ER) stress in the TM of Tg-MYOCY437H mice. Furthermore, topical PBA reduced IOP elevated by induction of ER stress via tunicamycin injections in WT mice.

Conclusions.: Topical ocular PBA reduces glaucomatous phenotypes in Tg-MYOCY437H mice, most likely by reducing myocilin accumulation and ER stress in the TM. Topical ocular PBA could become a novel treatment for POAG patients with myocilin mutations.

https://iovs.arvojournals.org/article.aspx?articleid=2188798

Gulab S. Zode, Kevin E. Bugge, Kabhilan Mohan, Sinisa D. Grozdanic, Joseph C. Peters, Demelza R. Koehn, Michael G. Anderson, Randy H. Kardon, Edwin M. Stone, Val C. Sheffield; Topical Ocular Sodium 4-Phenylbutyrate Rescues Glaucoma in a Myocilin Mouse Model of Primary Open-Angle Glaucoma. Invest. Op...

09/16/2023

WHERE TO PURCHASE - CONTACT US TO ORDER SODIUM PHENYLBUTYRATE

We are the exclusive worldwide supplier of sodium phenylbutyrate for researchers, labs, and compounding pharmacies.

LAB HOUSES

Scandinavian Formulas, Inc. supplies sodium phenylbutyrate to lab houses for their clinical/research customers. Contact us today to place an order.

Scandinavian Formulas, Inc. is the exclusive worldwide supplier of sodium phenylbutyrate to lab houses. Your lab house can subdivide quantities of sodium phenylbutyrate to supply to researchers in the smaller quantities the require.

COMPOUNDING PHARMACIES & PHARMA

We are the global supplier of sodium phenylbutyrate for compounding pharmacies that formulate sodium phenylbutyrate for researchers’ clinical supplies.

Does your compounding pharmacy need sodium phenylbutyrate to create a compound for clinical studies? Scandinavian Formulas, Inc. is the exclusive worldwide supplier of sodium phenylbutyrate for compounding pharmacies.

PATIENTS

At Scandinavian Formulas, Inc., we are sodium phenylbutyrate suppliers to sponsors of clinical investigations which are the subject of an investigational new drug (NDA).

Are you a patient looking for sodium phenylbutyrate suppliers?

Scandinavian Formulas does not supply sodium phenylbutyrate as a treatment. Physicians may wish to review the published list of clinical studies listed on this website to learn where studies are being/have been conducted. Scandinavian Formulas can assist in finding sponsors of various studies.

https://sodiumphenylbutyrate.com/order-sodium-phenylbutyrate/

08/31/2023

SODIUM PHENYLBUTYRATE CANCER RESEARCH

Sodium phenylbutyrate affects glutamine depletion and cell differentiation in cancer cells, as shown in cancer research studies.

Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and endoplasmic reticulum stress inhibitor in various diseases, including neurological diseases, inflammatory disorders, and carcinogenesis. Since the early 1990s, sodium phenylbutyrate has been used in clinical studies worldwide. The results of these studies are extremely promising.

CANCER

Cancer, also called malignancy, is an abnormal growth of cells. There are more than 100 types of cancer, including breast cancer, skin cancer, lung cancer, colon cancer, prostate cancer, and lymphoma. Symptoms vary depending on the type. Cancer treatment may include chemotherapy, radiation, and/or surgery.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate-cancer/

07/07/2023

SODIUM PHENYLBUTYRATE ALS RESEARCH

Sodium phenylbutyrate ALS research studies are contributing to worldwide knowledge about ALS and have shown promising results including prolonged survival, regulated expression of anti-apoptotic genes, and a reduction in neuron loss.

Amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. Voluntary muscles produce movements like chewing, walking, and talking. The disease is progressive, meaning the symptoms get worse over time. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease.

ALS belongs to a wider group of disorders known as motor neuron diseases, which are caused by gradual deterioration and death of motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and muscles throughout the body. These motor neurons initiate and provide vital communication links between the brain and the voluntary muscles.

Messages from motor neurons in the brain, called upper motor neurons, are transmitted to motor neurons in the spinal cord and to motor nuclei of the brain, called lower motor neurons, and from the spinal cord and motor nuclei of the brain to a particular muscle or muscles.
In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch in spasms called fasciculations, and waste away. Eventually, the brain loses its ability to initiate and control voluntary movements.

Early symptoms of ALS usually include muscle weakness or stiffness. Gradually, all muscles under voluntary control are affected, and individuals lose their strength and the ability to speak, eat, move, and even breathe. Most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10% of people with ALS survive for 10 or more years.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate-als/

06/30/2023

SODIUM PHENYLBUTYRATE USES AND BACKGROUND

Sodium phenylbutyrate was originally developed for Johns Hopkins in the mid-80s as a treatment for inborn errors of urea synthesis metabolic disorders that result in severe mental and psychomotor retardation. In 1996, sodium phenylbutyrate became a viable treatment for urea cycle disorders and is available commercially worldwide for that indication.

Ongoing cancer research has revealed that sodium phenylbutyrate also targets the underlying molecular defects that cause cancer and switches on tumor suppressor genes. It has become a novel anti-cancer therapy that offers lower toxicity than traditional chemotherapy.

Today research continues into new and groundbreaking sodium phenylbutyrate uses including cancer, cystic fibrosis, sickle cell anemia, ALS, Parkinson’s disease, glaucoma, spinal muscular atrophy, tuberculosis, and more.

CHEMICAL STRUCTURE AND METABOLIC ACTION

In terms of its chemical structure, sodium phenylbutyrate is a sodium salt of an aromatic fatty acid composed of an aromatic ring and butyric acid. The chemical name for sodium phenylbutyrate is 4-phenylbutyric acid sodium salt.

Sodium phenylbutyrate may be taken orally or intravenously. It has a naturally salty and slightly bitter taste which may or may not be apparent in its final tablet or powder form.

Although sodium phenylbutyrate is synthetically manufactured, once in the body it is quickly metabolized into a naturally occurring metabolite of phenylalanine. Because it is easily converted to a natural body substance, it has very low toxicity.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate-uses/

Sodium phenylbutyrate is used to treat urea cycle disorders in people who lack certain liver enzymes needed to eliminate waste substances from the body.

06/23/2023

SODIUM PHENYLBUTYRATE REDUCES REPETITIVE SELF-GROOMING BEHAVIOR AND RESCUES SOCIAL AND COGNITIVE DEFICITS IN MOUSE MODELS OF AUTISM

Abstract

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)–induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.

https://link.springer.com/article/10.1007/s00213-021-05812-z

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate...

06/12/2023

SODIUM PHENYLBUTYRATE AND ADRENOLEUKODYSTROPHY (ALD) RESEARCH

Sodium phenylbutyrate ALD research studies have shown promising results for adrenoleukodystrophy treatment.

Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 18,000 people. It most severely affects boys and men and knows no racial, ethnic, or geographic barriers. This brain disorder destroys myelin, the protective sheath that surrounds the brain’s neurons. The nerve cells that allow us to think and to control our muscles.

The most devastating form of ALD appears in childhood, generally between the ages of four and ten years old. Normal, healthy boys suddenly begin to regress. At first, they simply show behavioral problems, such as withdrawal or difficulty concentrating. Gradually, as the disease ravages their brain, their symptoms grow worse, including blindness and deafness, seizures, loss of muscle control, and progressive dementia. This relentless downward spiral leads to either death or permanent disability, usually within 2 to 5 years from diagnosis.

https://sodiumphenylbutyrate.com/adrenoleukodystrophy-treatment/

05/19/2023

MEDICAL FACILITIES USING SODIUM PHENYLBUTYRATE

Across the world, there are numerous medical and research facilities using sodium phenylbutyrate in clinical studies.

Clinical studies are in progress around the world using sodium phenylbutyrate to discover new things about a multitude of diseases and potential treatments. This includes sodium phenylbutyrate ALS studies, sodium phenylbutyrate cancer studies, and research into innovative new sodium phenylbutyrate uses.

Below is a list of medical facilities that are using or have used sodium phenylbutyrate in clinical research. Some facilities may be using related sodium phenylbutyrate formulations like triButyrate, phenylbutyric acid, sodium phenylbutyrate iv, or AMX0035.

United States

Auburn University
Baylor College of Medicine
Boston College
Children’s Hospital of Philadelphia
Cincinnati Children’s Hospital
Columbia University
Cornell
Harvard School of Public Health
Harvard University
Henderson Research Center
Thomas Jefferson University
Johns Hopkins
Mayo Foundation
North Texas Eye Institute
North Texas Health Center
Temple University Texas Southern University
University of Albany
University of Arkansas
University of CA – Irvine
University of CA – SF
University of Chicago
University of Colorado Health Science Center
University of Iowa
University of Michigan
University of Missouri
University of Texas – MD Anderson
Utah State University
VA Medical Center, Boston
Vanderbilt University Medical Center

International

Copenhagen University, Denmark
Hospital de Clínicas de Porto Alegre, Brazil
Karolinska Institute, Sweden
McGill University, Canada
McMaster University, Canada
Oxford University, UK
University of Alberta, Canada
University of BC, Canada
University of Madrid, Spain
University of Montreal, Canada
University of Munich, Germany

https://sodiumphenylbutyrate.com/medical-facilities/

04/26/2023

CLINICAL USE OF SODIUM PHENYLBUTYRATE

Sodium phenylbutyrate is contributing to the global health landscape through emerging research and clinical trials.

Refer to the clinical use of sodium phenylbutyrate in research and trial studies for the treatment of disorders such as cancer, ALS, ALD, and diabetes.

Copies of clinical trials are available upon request for these indications:
Addiction
Adrenoleukodystrophy (ALD)
Aging
Alzheimer’s disease
Amyotrophic lateral sclerosis (ALS)
Bladder dysfunction
Blood
Cancer
Cardiac injury
Cerebral ischemic injury
Cystic fibrosis
Diabetes
Endoplasmic reticulum stress
Epilepsy
Eye
Familial hypercholesterolemia
Spinal muscular atrophy
Urea cycle disorder/ornithine transcarbamylase deficiency
Huntington’s disease
Ischemic spinal cord damage
Kidney
Leucine metabolism
Lipoprotein receptor
Liver
Lung/abca3 defects
Maple syrup urine disease
Multiple sclerosis (MS)
Muscular Dystrophy
Obesity
Parkinson’s disease
Phenylketonuria
Rheumatoid arthritis
Schizophrenia
Sickle cell anemia, thalassemia, and Cooley’s anemia
Miscellaneous research and articles

https://sodiumphenylbutyrate.com/clinical-use-sodium-phenylbutyrate/

04/06/2023

SODIUM 4-PHENYLBUTYRATE REDUCES OCULAR HYPERTENSION BY DEGRADING EXTRACELLULAR MATRIX DEPOSITION VIA ACTIVATION OF MMP9

From: North Texas Eye Research Institute

Abstract
Ocular hypertension (OHT) is a serious adverse effect of the widely prescribed glucocorticoid (GC) therapy and, if left undiagnosed, it can lead to glaucoma and complete blindness. Previously, we have shown that the small chemical chaperone, sodium-4-phenylbutyrate (PBA), rescues GC-induced OHT by reducing ocular endoplasmic reticulum (ER) stress. However, the exact mechanism of how PBA rescues GC-induced OHT is not completely understood. The trabecular meshwork (TM) is a filter-like specialized contractile tissue consisting of TM cells embedded within extracellular matrix (ECM) that controls intraocular pressure (IOP) by constantly regulating aqueous humor (AH) outflow. Induction of abnormal ECM deposition in TM is a hallmark of GC-induced OHT. Here, we investigated whether PBA reduces GC-induced OHT by degrading abnormal ECM deposition in TM using mouse model of GC-induced OHT, ex vivo cultured human TM tissues and primary human TM cells. We show that topical ocular eye drops of PBA (1%) significantly lowers elevated IOP in mouse model of GC-induced OHT. Importantly, PBA prevents synthesis and deposition of GC-induced ECM in TM. We report for the first time that PBA can degrade existing abnormal ECM in normal human TM cells/tissues by inducing matrix metalloproteinase (MMP)9 expression and activity. Furthermore, inhibition of MMPs activity by chemical-inhibitor (minocycline) abrogated PBA’s effect on ECM reduction and its associated ER stress. Our study indicates a non-chaperone activity of PBA via activation of MMP9 that degrades abnormal ECM accumulation in TM.

https://www.mdpi.com/1422-0067/22/18/10095

Ocular hypertension (OHT) is a serious adverse effect of the widely prescribed glucocorticoid (GC) therapy and, if left undiagnosed, it can lead to glaucoma and complete blindness. Previously, we have shown that the small chemical chaperone, sodium-4-phenylbutyrate (PBA), rescues GC-induced OHT by r...

03/16/2023

HOW SODIUM PHENYLBUTYRATE WORKS

Sodium phenylbutyrate is metabolized safely and naturally, helping the kidneys eliminate wastes and controlling the expression of certain genes that may cause cancer and other diseases.

HOW SODIUM PHENYLBUTYRATE BENEFITS THE HUMAN BODY

Sodium phenylbutyrate is an approved treatment for people who have urea cycle disorders that allow nitrogen waste to build up in the blood plasma as ammonia glutamine, which is a condition known as hyperammonemia. When hyperammonemia persists in the body, it leads to mental disability, physical limitations, and early death.

Sodium phenylbutyrate encourages histone deacetylase (HDAC) enzymes to remove an acetyl group from histones, allowing them to bind DNA and inhibit gene transcription. HDAC is a family of 11 enzymes that may act as master regulators of many diseases by controlling gene expression.

The targets of HDAC enzymes are the acetyl (CH3CO) groups of histones. Histones are proteins that form a scaffold structure, around which a cell’s DNA is wrapped. Modification of these histone proteins by acetylation – the addition of acetyl groups – controls the tightness of the DNA around the histone proteins, thereby controlling the expression of the genes.

In cancer, for instance, increased HDAC expression results in deacetylation of histone proteins through the removal of acetyl groups. Deacetylation causes the DNA to be wrapped too tightly around the histones, thereby inhibiting gene expression. If the genes affected are tumor suppressor genes, cancer can result.

Today, the two main functions of sodium phenylbutyrate that are responsible for its effectiveness are glutamine depletion and cell differentiation.

GLUTAMINE DEPLETION

Glutamine is a non-essential amino acid and serves as the major nitrogen source for nucleic acid and protein synthesis. It is also an important energy substrate in rapidly-dividing cells. Tumor cells are significantly more sensitive to glutamine depletion than normal cells because they function on limiting levels of glutamine availability due to their increased utilization and accelerated catabolism.

Sodium phenylbutyrate depletes the cells of glutamine without affecting the glutamine-utilizing enzymes. In its metabolized form, it is capable of conjugating glutamine to yield phenyl acetyl glutamine (PAG), which is then excreted in the urine. This means the tumor cells will not have enough fuel to continue growing and multiplying.

Normal cells are not affected by the recommended dosages of sodium phenylbutyrate. It has been shown that sodium phenylbutyrate arrests tumor growth and induces differentiation of premalignant and malignant cells through its non-toxic mechanism.

CELL DIFFERENTIATION

Phenylbutyrate has been shown to be a non-toxic differentiation inducer, promoting maturation of various types of malignant cells. This is a good thing for the human body because maturation makes the cells less aggressive, causing them to cease dividing and eventually die.

Differentiation therapy also holds therapeutic potential for other diseases such as inherited anemias. Some exceptional results have been shown in the use of phenylbutyrate in sickle cell anemia/thalassemia, where it works by raising the HbF levels.

In-vitro studies of cystic fibrosis have shown encouraging results where phenylbutyrate restored missing cellular protein.

SODIUM PHENYLBUTYRATE’S MECHANISMS OF ACTION IN THE BODY

Sodium phenylbutyrate is an aromatic fatty acid that inhibits histone deacetylase by binding non-competitively to the enzyme and preventing it from binding to its substrate. It is metabolized to phenylacetate, with which it shares HDAC inhibitory activity and high levels of brain bioavailability.

Phenylacetate is rapidly metabolized to phenylacetylglutamine, a reaction that scavenges glutamines and underlies its efficacy in improving nitrogen clearance. Because an additional action of sodium phenylbutyrate is peroxisome proliferation with improved fatty acid oxidation rates, it is also being examined in peroxisome biogenesis disorders such as adrenoleukodystrophy. In homozygous beta thalassemia, sodium phenylbutyrate is used to increase gamma-globulin and hemoglobin transcription, presumably through its activity as an HDAC inhibitor.

PHARMACOKINETICS

In terms of the pharmacokinetics, plasma bioavailability of sodium phenylbutyrate was comparable when given orally or intravenously. In urea cycle disorders, the recommended adult oral doses of sodium phenylbutyrate are 9.9 to 13 g/m2/day. Peak serum levels occur approximately one hour after oral doses. The elimination half-life is 48 minutes and is independent of the dose.

Sodium phenylbutyrate exhibits nonlinear elimination kinetics and is eliminated primarily in urine as phenylacetylglutamine. It crosses the blood-brain barrier and intravenous dosing in non-human primates showed excellent cerebrospinal fluid (CSF) pe*******on with a median half-life of 132 minutes.

SAFETY AND CLINICAL USE IN HUMANS

Sodium phenylbutyrate is approved by the FDA for use in hyperammonemia due to urea cycle disorders. The drug has also been used in the long-term treatment of patients with ornithine transcarbamylase deficiency at the median dose of 352 mg/kg per day for an average of 26 months. Long-term use in this population is well tolerated.

The most common adverse effects of sodium phenylbutyrate are menstrual irregularities in female patients, reduced appetite, body odor, and a bad taste in the mouth. Other effects include liver function test abnormalities, weight gain, edema, abdominal pain, nausea, vomiting, headache, and skin rash. Irregular me**es occurred in 23% of patients. Approximately 4% of patients discontinued due to taste disturbance and/or loss of appetite.

Sodium phenylbutyrate is under development as an anti-cancer agent because of its activity as an HDAC inhibitor causing tumor differentiation, growth arrest, and apoptosis. Aplastic anemia has been associated with phenylbutyrate therapy in one patient with urea cycle disorders, although a causal relationship is unproven.

Similarly, occasional instances of anemia, leukopenia, leukocytosis, and thrombocytopenia and rare cases of thrombocytosis have been observed during therapy, but have not been directly associated with the drug. Arrhythmias and syncope have occurred rarely in patients treated with sodium phenylbutyrate, but a direct drug effect has not been shown.

In a dose-escalation study in patients with refractory solid tumor malignancies, doses of up to 45 g/day were administered. Due to dose-limiting toxicities, the study concluded that 27 g/day was the maximally tolerated dose. Nausea, vomiting, hypocalcemia, and fatigue occurred at the 36g/day and 45g/day doses. Gastrointestinal upset including nausea, dyspepsia, and vomiting occurred at the lowest dose of 9g/day and was seen within 30 minutes of drug ingestion. However, 82% of patients completed the study despite these side effects.

Other frequently reported side effects include a sweat-like odor, usually noticeable only to the caregiver. Mild neurotoxicity, including confusion and lethargy, has been noted at higher doses of close to 30g/day but resolved with dose reduction.

A dose-escalation study of intravenous sodium phenylbutyrate in patients with myelodysplastic syndromes and acute myelogenous leukemia found a maximally-tolerated dose at 375 mg/kg/day (26.3 g/day for a 70 kg individual) with no serious toxicities detected in patients receiving doses between 125 and 375 mg/kg/day (8.8 and 26.3 g/day for a 70 kg individual). Dose-limiting toxicities like lethargy, confusion, and slurred speech were detected at 440 and 500 mg/kg/day sodium phenylbutyrate (30.8 and 35 g/day respectively, for a 70 kg individual).

Reports of edema have been blamed on the high sodium load associated with the drug. Phase I/I I studies in subjects with sickle cell anemia, beta thalassemia, and adrenoleukodystrophy report similar side effects. Another phase I study in patients with refractory solid tumors tested intravenous sodium phenylbutyrate doses between 150 to 515 mg/kg/day (10 to 36 g/day for a 70 kg individual) with dose-limiting toxicities like excessive somnolence, confusion, and electrolyte abnormalities resulting at a dose of 515 mg/kg/day (36.0 g/day for a 70 kg individual).

The maximally tolerated dose of sodium phenylbutyrate was determined to be 410 mg/kg/day (28.7 g/day for a 70 kg individual) as there were no dose-limiting toxicities at this dose and no patients required dose-reductions or escalations. Although there have been normal pregnancies on sodium phenylbutyrate, there remains a concern about possible teratogenic effects.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate/