Chemical Property of Cyclosporine A
Chemical Property:
- Appearance/Colour:White Powder
- Vapor Pressure:0mmHg at 25°C
- Melting Point:148-151°C
- Refractive Index:1.467
- Boiling Point:1293.8 °C at 760 mmHg
- PKA:13.32±0.70(Predicted)
- Flash Point:736.3 °C
- PSA：278.80000
- Density:1.016 g/cm3
- LogP:4.14950
- Storage Temp.:2-8°C
- Solubility.:ethanol: 30 mg/mL
- Water Solubility.:Soluble in dimethyl sulfoxide and ethanol. Insoluble in water.
- XLogP3:7.5
- Hydrogen Bond Donor Count:5
- Hydrogen Bond Acceptor Count:12
- Rotatable Bond Count:15
- Exact Mass:1201.84136802
- Heavy Atom Count:85
- Complexity:2330
- Purity/Quality:
-
98.5% *data from raw suppliers
Cyclosporin A *data from reagent suppliers
Safty Information:
- Pictogram(s):
T， 
Xn
- Hazard Codes:T,Xn,F
- Statements:
45-60-22-40-36-20/21/22-11
- Safety Statements:
53-45-36/37-24/25-22-26-16
- MSDS Files:
-
SDS file from LookChem
Total 1 MSDS from other Authors
Useful:
- Canonical SMILES:CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)C(C(C)CC=CC)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C
- Isomeric SMILES:CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)N[C@@H](C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)[C@@H]([C@H](C)C/C=C/C)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C
- Recent ClinicalTrials:A Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Kidney Transplant Recipients Aged 12 to <18 Years to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications
- Recent EU Clinical Trials:A Prospective, Open-label, Multicenter, Randomized Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Renal Allograft Recipients Aged 12 to Less Than 18 Years of Age to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications
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Indications
For prevention of a variety of tissue and organ transplant rejection and treatment of some autoimmune diseases, also used in kidney disease, aplastic anemia, refractory ulcerative colitis. In dermatology, for stubborn and intractable skin diseases, the best effect is severe psoriasis (including vulgaris, pustular, erythrodermic and joint disease); good efficacy on skin disorders including Behcet disease, gangrenous pyoderma, lichen planus, acquired epidermolysis bullosa psychosis; moderate efficacy on disease including alopecia, atopic dermatitis, chronic actinic dermatitis, light class of reticulocyte cell histiocytosis, adult linear IgA bullous dermatitis, pemphigus, bullous pemphigoid (the latter two illness should be in combination with corticosteroids). In addition, Cyclosporine A has effect on systemic lupus erythematosus, dermatomyositis, systemic sclerosis, AIDS, ichthyosis, cutaneous T-cell lymphoma, pityriasis rubra pilaris, generalized missed acrodermatitis, palmoplantar pus blister disease, male pattern baldness, vitiligo, progressive necrotizing xanthogranulomatous, generalized granuloma annulare, lichen myxedema, papular mucin calm disease, hyperthyroidism.
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Drug interactions
1, In addition to corticosteroids, this product should be avoided in combination with any other immunosuppressive agents.
2, The inactivation of product is mainly in the liver metabolic, any drugs which can affect the liver enzyme activities can affect the metabolism of the product, such as erythromycin, josamycin, doxycycline, ketoconazole, H2 receptor antagonists , calcium antagonists, androgens, oral contraceptives affect activity of cytochrome P-450 liver cell, increase the risk of toxicity of this product.
3, Carbamazepine, phenytoin, phenobarbital, isoniazid, rifampin, et al. can make the plasma concentration of this product decrease.
4, Aminoglycoside antibiotic, trimethoprim-sulfamethoxazole, TMP, amphotericin B, cephalosporins, mechlorethamine, nonsteroidal anti-inflammatory drug, mannitol, furosemide, et al increase nephrotoxicity of cyclosporine .
5, Calcium and increased calcium are disabled when using this product, and cannot be vaccinated.
6, Long-term in combination with glucocorticoid can trigger diabetes, hypertension, ulcer disease and osteoporosis, and can increase the toxicity of this product.
7, Before used Cyclosporin A, other immunosuppressive agents are used, patients have overall decreased immunity and are easy to be infected. Potentially hazardous interactions with other drugs
Increased risk of hyperkalaemia with ACE
inhibitors, angiotensin-II antagonists, potassiumsparing diuretics, potassium salts.
Increased risk of nephrotoxicity with
aminoglycosides, amphotericin, co-trimoxazole,
disopyramide, foscarnet, melphalan, NSAIDs,
polymyxins, quinolones, sulphonamides, thiazide
diuretics, trimethoprim and vancomycin.
Increased ciclosporin levels with acetazolamide,
aciclovir, amiodarone, atazanavir, boceprevir,
carvedilol, chloramphenicol, chloroquine, cimetidine,
danazol, diltiazem, doxycycline, famotidine,
fluconazole, fluoxetine, fluvoxamine, fosamprenavir,
glibenclamide, glipizide, grapefruit juice,
hydroxychloroquine, imatinib, indinavir, itraconazole,
ketoconazole, lercanidipine (concentration of both
drugs increased - avoid), macrolides, micafungin,
miconazole, high-dose methylprednisolone,
metoclopramide, metronidazole, muromonabCD3, nicardipine, posaconazole, progestogens,
propafenone, ritonavir, saquinavir and telaprevir
(concentration of both drugs increased), tacrolimus,
verapamil and voriconazole.
Decreased ciclosporin levels with barbiturates,
bupropion, carbamazepine, efavirenz, fosphenytoin,
griseofulvin, lanreotide, modafinil, octreotide,
pasireotide, phenytoin, primidone, quinine, red
wine, rifampicin, St John’s wort, sulfadiazine,
IV sulfadimidine, sulfasalazine, sulfinpyrazone,terbinafine, ticlopidine and IV trimethoprim and
possibly by oxcarbazepine.Aliskiren: concentration of aliskiren increased -
avoid.
Ambrisentan: concentration of ambrisentan
increased.
Antibacterials: increased risk of myopathy with
daptomycin - try to avoid concomitant use.
Anticoagulants: concentration of dabigatran and
edoxaban increased - avoid with dabigatran and
reduce dose of edoxaban.
Antidiabetics: may increase repaglinide
concentration, risk of hypoglycaemia.
Antimuscarinics: avoid with darifenacin.
Antivirals: avoid with simeprevir, increased
simeprevir concentration; when starting coadministration with dasubavir and ombitasvir/
paritaprevir/ritonavir, give one fifth of the total daily
dose of ciclosporin once daily. Monitor ciclosporin
levels and adjust dose and/or dosing frequency as
needed.
Basiliximab: may alter ciclosporin levels.
Bosentan: co-administration of ciclosporin and
bosentan is contraindicated. When ciclosporin
and bosentan are co-administered, initial trough
concentrations of bosentan are 30 times higher
than normal. At steady state, trough levels are 3-4
times higher than normal. Blood concentrations of
ciclosporin decreased by 50%.
Calcium-channel blockers: increased nifedipine
concentration and toxicity; amlodipine may increase
ciclosporin concentration by up to 40%.
Cardiac glycosides: increased digoxin concentration
and toxicity.
Caspofungin: caspofungin concentration increased -
monitor LFTs.
Colchicine: risk of myopathy or rhabdomyolysis;
also increased blood-ciclosporin concentrations and
nephrotoxicity - avoid.
Cytotoxics: increased risk of neurotoxicity
with doxorubicin; concentration of epirubicin,
everolimus and idarubicin increased; reduced
excretion of mitoxantrone; increased toxicity with
methotrexate; seizures have been reported in bone
marrow transplant patients taking busulfan and
cyclophosphamide; use crizotinib with caution;
concentration of etoposide possibly increased
(increased risk of toxicity); possible interaction with
docetaxol.
Eltrombopag: exposure reduced by ciclosporin.
Fidaxomicin: avoid concomitant use.Lenalidomide: concentration of lenalidomide
increased.
Lipid-lowering agents: absorption reduced by
colesevelam, increased risk of myopathy with statins
(avoid with simvastatin, max dose of atorvastatin
should be 10 mg1
); avoid with rosuvastatin; increased
risk of nephrotoxicity with fenofibrate; bezafibrate
may increase creatinine and reduce ciclosporin levels;
concentration of both drugs may be increased with
ezetimibe.
Mycophenolate mofetil: some studies show that
ciclosporin decreases plasma MPA AUC levels - no
dose change required.
NSAIDs: diclofenac concentration increased -
reduce diclofenac dose.
Omeprazole: may alter ciclosporin concentration.
Orlistat: absorption of ciclosporin possibly reduced.
Prednisolone: increased prednisolone concentration.
Rifaximin: concentration of rifaximin increased.
Sirolimus: increased absorption of sirolimus -
give sirolimus 4 hours after ciclosporin; sirolimus
concentration increased; long term concomitant
administration may be associated with deterioration
in renal function.
Tacrolimus: increased ciclosporin concentration and
toxicity - avoid.
Ursodeoxycholic acid: unpredictably increased
absorption and raised ciclosporin levels in some
patients.
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Description
Cyclosporine A is a powerful immunosuppressive drug intended for preventing rejection
of kidney, heart, and lung transplants.
A new era in the development of immunopharmacology began with the discovery of
cyclosporines.
Cyclosporines are produced by mycelial mushrooms Tolypocladium inflatum,
Tricoderma polysporum, and Cylindrocarpon lucidum, which are found in the ground.Cyclosporine A is the first drug to affect a specific line of protecting cells of the body.
Unlike usual cytotoxics, it suppresses T-cells and acts on all cell lines simultaneously.
Cyclosporine A significantly eases the ‘reception’ of transplants, and increases the possibility of treating autoimmune system diseases.
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Uses
An immunosuppressant that has revolutionized organ transplantation through its use in the prevention of graft rejection.
A group of nonpolar cyclic oligopeptides with immunosupppressant activity. prothrombogenic agent Cyclosporin A is a hydrophobic cyclic peptide isolated from several fungal species including Cylindrocarpon, Fusarium, Trichoderma and Tolypocladium. Cyclosporin A inhibits T-cell activation and has been marketed since 1983 as an immunosuppressant in post-allogeneic organ transplant. Cyclosporin A acts by binding to the protein, cyclophilin (immunophilin), in T-lymphocytes causing inhibition of calcineurin (protein phosphatase 2B). Cyclosporin A reduces transcription of interleukin 2, and inhibits lymphokine production, interleukin release and NO synthesis induced by interleukin 1α, lipopolysaccharides and TNFα.
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Clinical Use
Immunosuppressant:
Prophylaxis of solid organ transplant rejection
Nephrotic syndrome
Atopic dermatitis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
