ミコフェノール酸

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

Pharmaceutical

Pharmaceuticals

Pharmaceuticals -> Metabolite of Mycophenolate mofetil

Pharmaceuticals -> Antibiotics

2.8

2.76

Insoluble

3.55e-02 g/L

141°C

141 °C

165.4 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

176 Ų [M+NH4]+ [CCS Type: TW; Method: calibrated with polyalanine]

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P270, P273, P280, P301+P317, P318, P319, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 89 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Status: Active Update: 07-09-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/15977

4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, (4E)-: Does not have an individual approval but may be used under an appropriate group standard

Mycophenolic acid 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, mycophenolic acid has potent cytostatic effects on lymphocytes. Mycophenolic acid inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of mycophenolic acid on lymphocytes. Mycophenolic acid also suppresses antibody formation by B-lymphocytes. Mycophenolic acid 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.

L04AA06

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Mycophenolic acid is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) that blocks _de novo_ biosynthesis of purine nucleotides. This affects lymphocytes primarily and leads to the suppression of DNA synthesis in T- and B-cells. Mycophenolic acid arrests the T-lymphocyte cell cycle at the G1/S interface and inhibits the proliferation of lymphocytes. Also, it has been suggested that mycophenolic acid suppresses cytokine production by limiting the number of cytokine-producing cells. The enteric-coating of mycophenolic acid tablets prevents the development of upper gastrointestinal adverse events by delaying drug release until it reaches the small intestine. Patients treated with mycophenolic acid have a higher risk of developing new or reactivated viral infections, serious infections, blood dyscrasias (including pure red cell aplasia), serious gastrointestinal tract complications, acute inflammatory syndrome associated with mycophenolate products, lymphoma, and other malignancies. The use of mycophenolic acid is also associated with an increased risk of first-trimester pregnancy loss and congenital malformations. Mycophenolic acid should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT). Patients treated with mycophenolic acid should not receive live attenuated vaccines or donate blood or semen.

Mycophenolic acid is a selective noncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), that blocks the conversion of inosine-5-phosphate and xanthine-5-phosphate to guanosine-5-phosphate. By inhibiting IMPDH, mycophenolic acid interferes with the _de novo_ pathway of guanosine nucleotide synthesis without incorporation into DNA. While other cell types are able to use salvage pathways, T- and B-lymphocyte proliferation is a mechanism heavily dependent on the _de novo_ synthesis of purines. Therefore, mycophenolic acid has potent cytostatic effects on T- and B- and lymphocytes. Mycophenolic acid also suppresses antibody formation by B-lymphocytes and prevents the glycosylation of lymphocyte and monocyte glycoproteins involved in intercellular adhesion to endothelial cells.

Mycophenolic acid is mainly metabolized by glucuronyl transferase to form glucuronidated metabolites. Mycophenolic acid glucuronide (MPAG), the major metabolite of mycophenolic acid, does not display pharmacological activity. However, the acyl glucuronide minor metabolite has a pharmacological activity similar to mycophenolic acid. The AUC ratio of mycophenolic acid:MPAG:acyl glucuronide is approximately 1:24:0.28 at a steady state.

Mycophenolic acid has known human metabolites that include 6-O-desmethyl-MPA (DM-MPA) and Mycophenolic acid glucuronide.

Mycophenolic acid is metabolized mainly by glucuronyl transferase to glucuronidated metabolites, predominantly the phenolic glucuronide, mycophenolic acid glucuronide (MPAG). MPAG does not manifest pharmacological activity. The acyl glucuronide minor metabolite has pharmacological activity similar to mycophenolic acid. The AUC ratio of Mycophenolic acid:MPAG:acyl glucuronide is approximately 1:24:0.28 at steady state. Half Life: The mean elimination half-life for mycophenolic acid ranges from 8-16 hours, while that of the MPAG metabolite ranges from 13-17 hours.

HU9DX48N0T

MYCOPHENOLIC ACID

Established Pharmacologic Class [EPC] - Antimetabolite Immunosuppressant

Mycophenolic acid is an Antimetabolite Immunosuppressant.

MYCOPHENILIC ACID

Antimetabolite Immunosuppressant [EPC]

Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.

Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Between 360 mg and 2,160 mg, mycophenolic acid follows a linear and dose-proportional pharmacokinetic profile. The enteric-coating of mycophenolic acid tablets prevents release under acidic conditions (stomach, pH < 5). However, enteric-coated mycophenolic acid tablets are highly soluble in neutral pH conditions such as those in the intestine. In renal transplant patients, the median delay (Tlag) in the rise of mycophenolic acid concentration ranged between 0.25 and 1.25 hours, and the Tmax ranged between 1.5 and 2.75 hours. Adult renal transplant patients on cyclosporine given mycophenolic acid had a Tmax of 2 h, a Cmax of 26.1 μg/mL, and an AUC0-12 of 66.5 μg⋅h/mL. Stable pediatric (5-16 years old) renal transplant patients had a Cmax and AUC 33% and 18% higher than the ones detected in adults. In stable renal transplant patients treated with cyclosporine, the gastrointestinal absorption and absolute bioavailability of delayed-release tablets of mycophenolic acid were 93% and 72%, respectively. Following the administration of a high-fat meal (55 g fat, 1000 calories), the AUC of mycophenolic acid (enteric-coated tablets, 720 mg) was comparable to the one detected during fasting. However, a high-fat meal can lead to a 33% decrease of the Cmax, a 3.5-hour delay in the Tlag (range of -6 to 18 hours), and a 5.0-hour delay in the Tmax (range of -9 to 20 hours). To avoid variability in the absorption of mycophenolic acid, this drug should be taken on an empty stomach.

In stable renal transplant patients, approximately 60% of mycophenolic acid is eliminated in the urine as mycophenolic acid glucuronide (MPAG), while 3% is eliminated unchanged. MPAG is also secreted in the bile and is available for deconjugation by gut flora. The mycophenolic acid that results from MPAG deconjugation may be reabsorbed and produce a second peak 6-8 hours after administration.

At steady state, the volume of distribution of mycophenolic acid is 54 L. At the elimination phase, the volume of distribution of mycophenolic acid is 112 L.

The mean clearance of mycophenolic acid is 140 mL/min. The mean renal clearance of its metabolite, mycophenolic acid glucuronide, is 15.5 mL/min.

Use (kg; approx.) in Germany (2009): ?2500

For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.