Tìm theo
Mycophenolate mofetil
Các tên gọi khác (5 ) :
  • 2-Morpholinoethyl (e)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate
  • Cellcept
  • MMF
  • Mycophenolic acid morpholinoethyl ester
  • RS 61443
Thuốc Gốc
Small Molecule
CAS: 128794-94-5
ATC: L04AA06
ĐG : Accord Healthcare , http://www.accord-healthcare.com
CTHH: C23H31NO7
PTK: 433.4947
Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent, inosine monophosphate dehydrogenase (IMPDH) inhibitor.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C23H31NO7
Phân tử khối
433.4947
Monoisotopic mass
433.210052351
InChI
InChI=1S/C23H31NO7/c1-15(5-7-19(25)30-13-10-24-8-11-29-12-9-24)4-6-17-21(26)20-18(14-31-23(20)27)16(2)22(17)28-3/h4,26H,5-14H2,1-3H3/b15-4+
InChI Key
InChIKey=RTGDFNSFWBGLEC-SYZQJQIISA-N
IUPAC Name
2-(morpholin-4-yl)ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
Traditional IUPAC Name
mycophenolate mofetil
SMILES
COC1=C(C\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C
Độ hòa tan
Slightly soluble (43 mg/mL at pH 7.4)
logP
2.5
logS
-3.7
pKa (strongest acidic)
9.76
pKa (Strongest Basic)
6.19
PSA
94.53 Å2
Refractivity
117.1 m3·mol-1
Polarizability
45.55 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
6
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA), an antibiotic substance derived from Penicillium stoloniferum. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites.
Cơ Chế Tác Dụng : Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent, inosine monophosphate dehydrogenase (IMPDH) inhibitor. Mycophenolate mofetil is hydrolyzed to form mycophenolic acid (MPA), which is the active metabolite. MPA is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes. MPA inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B-lymphocytes. MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. Mycophenolate mofetil did not inhibit early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 (IL-1) and interleukin-2 (IL-2), but did block the coupling of these events to DNA synthesis and proliferation.
Dược Động Học :
▧ Absorption :
Rapidly absorbed following oral administration. In 12 healthy volunteers, the mean absolute bioavailability of oral mycophenolate mofetil relative to intravenous mycophenolate mofetil (based on MPA AUC) was 94%. The absolute bioavailability of the delayed release tablet in stable renal transplant patients on cyclosporin is 72%. Food (27 g fat, 650 calories) has no effect on the extent of absorption (MPA AUC) of mycophenolate mofetil.
▧ Volume of Distribution :
* 3.6 ±1.5 L/kg [intravenous, healthy subjects, MPA] * 4 ±1.2 L/kg [oral administration, healthy subjects, MPA]
▧ Protein binding :
MPA (the active metabolite), at clinically relevant concentrations, is over 98% bound to plasma albumin. The phenolic glucuronide of MPA, mycophenolic acid glucuronide (MPAG) has 82% protein bound.
▧ Metabolism :
Following oral and intravenous dosing, mycophenolate mofetil undergoes complete metabolism to MPA, the active metabolite. Metabolism to MPA occurs presystemically after oral dosing. MPA is metabolized principally by glucuronyl transferase to form the phenolic glucuronide of MPA (MPAG) which is not pharmacologically active. In vivo, MPAG is converted to MPA via enterohepatic recirculation. The following metabolites of the 2-hydroxyethyl-morpholino moiety are also recovered in the urine following oral administration of mycophenolate mofetil to healthy subjects: N-(2-carboxymethyl)-morpholine, N-(2-hydroxyethyl)-morpholine, and the N-oxide of N-(2-hydroxyethyl)-morpholine. Cytochrome P450 isozymes, CYP3A4/5 and to a lesser extent by CYP2C8, is responsible for the biotransformation of MPA to 6-O-desmethyl-mycophenolic acid.
▧ Route of Elimination :
Negligible amount of drug is excreted as MPA (< 1% of dose) in the urine. When orally administered, mycophenolate mofetil was completely recovered with 93% of the dose found in the urine and 6% found in feces. 87% of the administered dose is excreted in the urine as MPAG.
▧ Half Life :
The mean elimination half-life for mycophenolic acid (the active metabolite) ranges from 8-16 hours, while that of the MPAG metabolite ranges from 13-17 hours.
▧ Clearance :
* 193 mL/min [plasma clearance, MPA, oral administration] * 177 mL/min [plasma clearance, MPA, IV administration] * 15.5 mL/min [renal clearance, MPAG, delayed-release tablet]
Độc Tính : Oral (LD50): Acute: 352 mg/kg [Rat], 1000 mg/kg [Mouse], and >6000 mg/kg [Rabbit]. Possible signs and symptoms of acute overdose could include the following: hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia.
Chỉ Định : For the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. Mycophenolate mofetil should be used concomitantly with cyclosporine and corticosteroids.
Tương Tác Thuốc :
  • Belatacept Belatacept increases the Cmax and AUC of mycophenolate mofetil.
  • Calcium Formation of non-absorbable complexes
  • Iron Oral iron decreases the absorption of mycophenolate-mofetil
  • Iron Dextran Oral iron decreases the absorption of mycophenolate-mofetil
  • Rifampicin Rifampin may decrease the serum concentration of mycophenolate. Concomitant therapy should be avoided.
  • Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
  • Tacrolimus Tacrolimus may increase the plasma concentration of Mycophenolic acid. Monitor and adjust the dose of Mycophenolate mofetil to the therapeutic range.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Valganciclovir The excretion rates of Valganciclovir and/or Mycophenolate mofetil may decrease. Monitor for increased serum concentrations and toxicity of both agents.
Liều Lượng & Cách Dùng : Capsule - Oral - 250 mg
Injection, powder, for solution - Intravenous - 500 mg
Suspension - Oral - 200 mg/mL
Tablet - Oral - 500 mg
Tablet, delayed release - Oral - 180 mg, 360 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00688
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5281078
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505626
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07908
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00752
ChemSpider
http://www.chemspider.com/Chemical-Structure.4444535.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0781-2067-01
PharmGKB
http://www.pharmgkb.org/drug/PA450566
Wikipedia
http://en.wikipedia.org/wiki/Mycophenolate_mofetil
RxList
http://www.rxlist.com/cgi/generic3/cellcept.htm
Drugs.com
http://www.drugs.com/cdi/mycophenolate-mofetil.html
... loading
... loading