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

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

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

Công ty : Hyperion Therapeutics, Inc.

Sản phẩm biệt dược : Ravicti

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

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