| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 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 phenylbutyrate (PBA) is released from the glycerol backbone by lipases in the gastrointestinal tract. PBA then undergoes beta-oxidtion to form PAA. When a single oral dose of 2.9 mL/m2 of Glycerol phenylbutyrate is given to fasting adult subjects, the pharmacokinetic parameters are 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, the hydrolysis of glycerol phenylbutyrate is incomplete, but to what extent is unknown. When glycerol phenylbutyrate is given to adult UCD patients, maximum plasma concentrations at steady state (Cmaxss) of PBA, PAA, and PAGN occurred at 8 h, 12 h, and 10 h, respectively, after the first dose in the day. Intact glycerol phenylbutyrate was not detectable in plasma in UCD patients. Glycerol phenylbutyrate is mainly excreted as PAGN in the urine (68.9% in adults and 66.5% in pediatric UCD patients). PAA and PBA represented minor urinary metabolites, each accounting for <1% of the administered dose of PBA. Metabolism / Metabolites Pancreatic lipases hydrolyze glycerol phenylbutyrate to release PBA from the glycerol backbone. PBA undergoes β-oxidation to PAA, which is conjugated with glutamine in the liver and in the kidney through the enzyme 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 molecules of phenylbutyrate are linked to a glycerol backbone. FDA approved on February 1, 2013. See also: Phenylbutyric acid (has active moiety). Drug Indication Glycerol phenylbutyrate is a nitrogen-binding agent for the chronic management of adult and pediatric patients ≥2 years of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. FDA Label Ravicti is indicated for use as adjunctive therapy for chronic management of patients with urea cycle disorders (UCDs) including deficiencies of carbamoyl phosphate-synthase-I (CPS), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL), arginase I (ARG) and ornithine translocase deficiency hyperornithinaemia-hyperammonaemia homocitrullinuria syndrome (HHH) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Ravicti must be used with dietary protein restriction and, in some cases, dietary supplements (e. g. , essential amino acids, arginine, citrulline, protein-free calorie supplements). Treatment of urea cycle disorders Mechanism of Action The toxic accumulation of ammonia in the blood and brain arise from urea cycle disorders in which patients are deficient in critical enzymes or transporters that are involved in the synthesis of urea from ammonia. Glycerol phenylbutyrate is a prodrug - the major metabolite, phenylacetate (PAA) is the molecule that binds to nitrogen. PAA conjugates with glutamine (which contains 2 molecules of nitrogen) via acetylation in the liver and kidneys to form phenylacetylglutamine (PAGN), which is excreted by the kidneys. PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion. Pharmacodynamics Glycerol phenylbutyrate prolongs the QTc interval. |
| 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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