Tìm theo
Glycerol Phenylbutyrate
Các tên gọi khác (4 ) :
  • Glyceryl Tri-4-Phenylbutyrate
  • GPB
  • HPN100
  • Ravicti
ammonia detoxicants
Thuốc Gốc
Small Molecule
CAS: 611168-24-2
ATC: A16AX09
CTHH: C33H38O6
PTK: 530.6512
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C33H38O6
Phân tử khối
530.6512
Monoisotopic mass
530.266838948
InChI
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
InChI Key
InChIKey=ZSDBFLMJVAGKOU-UHFFFAOYSA-N
IUPAC Name
1,3-bis[(4-phenylbutanoyl)oxy]propan-2-yl 4-phenylbutanoate
Traditional IUPAC Name
1,3-bis[(4-phenylbutanoyl)oxy]propan-2-yl 4-phenylbutanoate
SMILES
O=C(CCCC1=CC=CC=C1)OCC(COC(=O)CCCC1=CC=CC=C1)OC(=O)CCCC1=CC=CC=C1
Độ hòa tan
Insoluble
logP
7.65
logS
-7
pKa (Strongest Basic)
-6.6
PSA
78.9 Å2
Refractivity
149.74 m3·mol-1
Polarizability
60.16 Å3
Rotatable Bond Count
20
H Bond Acceptor Count
3
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
3
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Glycerol phenylbutyrate prolongs the QTc interval.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ Absorption :
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.
▧ Protein binding :
PBA = 80.6% to 98.0%; PAA = 37.1% to 65.6%; PAGN = 7% to 12%.
▧ Metabolism :
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.
▧ Route of Elimination :
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.
Độc Tính : Most common adverse reactions in ≥10% of patients are diarrhea, flatulence, and headache.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Haloperidol Haloperidol may induce hyperammonemia. Monitor ammonia levels closely when use of haloperidol is necessary in UCD patients.
  • Prednisone Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels. Monitor ammonia levels closely when corticosteroids and glycerol pehnylbutyrate are used concomitantly.
  • Probenecid Probenecid may inhibit the renal excretion of metabolites of glycerol phenylbutyrate including PAGN and PAA.
  • Valproic Acid Valproic acid may induce hyperammonemia. Monitor ammonia levels closely when use of valproic acid is necessary in UCD patients.
Liều Lượng & Cách Dùng : Liquid - Oral - 1.1 g/mL
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08909
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D10127
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/76325-100-25
Wikipedia
http://en.wikipedia.org/wiki/Glycerol_phenylbutyrate
RxList
http://www.rxlist.com/ravicti-drug.htm
Drugs.com
http://www.drugs.com/cdi/glycerol-phenylbutyrate.html
... loading
... loading