| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| ln Vivo |
GPB, or glyceryl phenylbutyrin, may be used to treat hyperammonemia. Therapeutic promise for other disorders such chronic hepatic encephalopathy or other inherited metabolic diseases may exist for glyceryl phenylbutyrin (GPB) [1][2].
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Glycerol phenylbutyrate is a prodrug in which phenylbutyric acid (PBA) is released from the glycerol backbone by lipases in the gastrointestinal tract. PBA then undergoes β-oxidation to phenylpropionic acid (PAA). When chlorhexidine chloride was administered orally in fasting adult subjects at a single dose of 2.9 mL/m², the pharmacokinetic parameters were as follows: Tmax: PBA = 2 hours; PAA = 4 hours; PAGN = 4 hours. Cmax: PBA = 37.0 µg/mL; PAA = 14.9 µg/mL; PAGN = 30.2 µg/mL. In healthy subjects, chlorhexidine chloride is incompletely hydrolyzed, but the extent of hydrolysis is unclear. When chlorhexidine chloride was administered to adult patients with urea cycle disorder (UCD), the steady-state peak plasma concentrations (Cmaxss) of PBA, PAA, and PAGN were reached at 8, 12, and 10 hours after the first dose of the day, respectively. Intact phenylbutyrate was not detected in the plasma of patients with UCD. Phenylene butyrate is primarily excreted in the urine as PAGN (68.9% in adults and 66.5% in children with UCD). PAA and PBA are minor urinary metabolites, each accounting for less than 1% of the administered PBA dose. Metabolism/Metabolites: Pancreatic lipases hydrolyze phenylbutyrate, releasing PBA from the glycerol backbone. PBA is β-oxidized to PAA, which is then conjugated with glutamine in the liver and kidneys by phenylacetyl-CoA:L-glutamine-N-acetyltransferase to form PAGN. |
| Toxicity/Toxicokinetics |
Protein Binding
PBA = 80.6% to 98.0%; PAA = 37.1% to 65.6%; PAGN = 7% to 12%. |
| References | |
| Additional Infomation |
Glycerol phenylbutyrate is a triglyceride. Glycerol phenylbutyrate is a nitrogen-binding agent. Chemically, it is a triglyceride in which three phenylbutyrate molecules are linked to a glycerol backbone. It was approved by the FDA on February 1, 2013. See also: Glycerol phenylbutyrate (containing the active ingredient). Drug Indications Glycerol phenylbutyrate is a nitrogen-binding agent used to treat long-term disease in adult and pediatric patients aged 2 years and older with urea cycle disorder (UCD) that is not effectively controlled by dietary protein restriction and/or amino acid supplementation alone. FDA Label Ravicti is indicated as adjunctive therapy for the treatment of long-term disease in patients with urea cycle disorder (UCD), including deficiencies in carbamoyl phosphate synthase-I (CPS), ornithine carbamoyltransferase (OTC), arginine succinate synthase (ASS), arginine succinate lyase (ASL), arginine enzyme I (ARG), and ornithine translocases, as well as hyperornithineemia-hyperammonemia. For patients with homocitrullinuria (HHH) that cannot be controlled by dietary protein restriction and/or amino acid supplementation alone, dietary protein restriction must be combined with supplementation, and in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements) are also necessary. Treatment of Urea Cycle Disorders Mechanism of Action Urea cycle disorders lead to the toxic accumulation of ammonia in the blood and brain. Patients lack key enzymes or transport proteins involved in ammonia synthesis of urea. Glyceryl phenylbutyrate is a prodrug—its main metabolite, phenylacetic acid (PAA), is a nitrogen-bound molecule. PAA binds to glutamine (containing 2 nitrogen molecules) in the liver and kidneys via acetylation to form phenylacetylglutamine (PAGN), which is excreted by the kidneys. PAGN, like urea, contains 2 moles of nitrogen, providing an alternative pathway for the excretion of waste nitrogen. Pharmacodynamics Glyceryl phenylbutyrate can prolong the QTc interval.
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| Molecular Formula |
C33H38O6
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|---|---|
| Molecular Weight |
530.661
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| Exact Mass |
530.267
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| Elemental Analysis |
C, 74.69; H, 7.22; O, 18.09
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| CAS # |
611168-24-2
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| PubChem CID |
10482134
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| Appearance |
Colorless to light yellow oil
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| LogP |
6.053
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
39
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| Complexity |
648
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CCCC1=CC=CC=C1)OC(COC(CCCC2=CC=CC=C2)=O)COC(CCCC3=CC=CC=C3)=O
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| InChi Key |
ZSDBFLMJVAGKOU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H38O6/c34-31(22-10-19-27-13-4-1-5-14-27)37-25-30(39-33(36)24-12-21-29-17-8-3-9-18-29)26-38-32(35)23-11-20-28-15-6-2-7-16-28/h1-9,13-18,30H,10-12,19-26H2
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| Chemical Name |
2,3-bis(4-phenylbutanoyloxy)propyl 4-phenylbutanoate
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| Synonyms |
HPN 100; HPN100; HPN-100; Glycerol phenylbutyrate, trade name: Ravicti;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~188.45 mM)
Ethanol : ~50 mg/mL (~94.22 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (4.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (4.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8844 mL | 9.4222 mL | 18.8445 mL | |
| 5 mM | 0.3769 mL | 1.8844 mL | 3.7689 mL | |
| 10 mM | 0.1884 mL | 0.9422 mL | 1.8844 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03335488 | COMPLETEDWITH RESULTS | Drug: RAVICTI Drug: NaPBA |
Urea Cycle Disorder | Amgen | 2018-02-20 | Phase 4 |
| NCT05019417 | UNKNOWN STATUS | Drug: Glycerol Phenylbutyrate 1100 MG/ML | Monocarboxylate Transporter 8 Deficiency | Kaplan Medical Center | 2021-06-30 | Phase 2 Phase 3 |
| NCT05983588 | RECRUITING | Drug: RAVICTI 1.1 g/ml Drug: Placebo |
Corticobasal Syndrome (CBS) | Technical University of Munich | 2023-12-12 | Phase 2 |
| NCT00977600 | COMPLETED | Drug: HPN-100 Drug: Ammonul Drug: Buphenyl |
Healthy | Amgen | 2005-03 | Phase 1 |
| NCT02323100 | TERMINATED | Drug: Ravicti low dose Drug: Ravicti high dose Drug: Placebo |
Cystic Fibrosis | National Jewish Health | 2018-12-02 | Phase 1 Phase 2 |
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