Tìm theo
Cyclosporine
Các tên gọi khác (4 ) :
  • Ciclosporin
  • CsA
  • CyA
  • Cyclosporin A
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 59865-13-3
ATC: L04AD01, S01XA18
ĐG : Abbott Laboratories Ltd. , http://www.abbott.com
CTHH: C62H111N11O12
PTK: 1202.6112
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Cyclosporine is produced as a metabolite by the fungus species Cordyceps militaris. (From Martindale, The Extra Pharmacopoeia, 30th ed).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C62H111N11O12
Phân tử khối
1202.6112
Monoisotopic mass
1201.841368071
InChI
InChI=1/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+
InChI Key
InChIKey=PMATZTZNYRCHOR-IMVLJIQENA-N
IUPAC Name
30-ethyl-33-[(4E)-1-hydroxy-2-methylhex-4-en-1-yl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-bis(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecone
Traditional IUPAC Name
cyclosporin A
SMILES
CCC1NC(=O)C(C(O)C(C)C\C=C\C)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C
Độ tan chảy
148-151 °C
Độ hòa tan
9.52e-03 g/l
logP
3.64
logS
-5.1
pKa (strongest acidic)
11.83
pKa (Strongest Basic)
-2.4
PSA
278.8 Å2
Refractivity
327.14 m3·mol-1
Polarizability
133.24 Å3
Rotatable Bond Count
15
H Bond Acceptor Count
12
H Bond Donor Count
5
Physiological Charge
0
Number of Rings
1
Bioavailability
0
caco2 Permeability
-6.05
Dược Lực Học : Used in immunosuppression for prophylactic treatment of organ transplants, cyclosporine exerts specific and reversible inhibition of immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T1-helper cell is the main target, although the T1-suppressor cell may also be suppressed. Sandimmune (cyclosporine) also inhibits lymphokine production and release including interleukin-2.
Cơ Chế Tác Dụng : A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Cyclosporine is produced as a metabolite by the fungus species Cordyceps militaris. (From Martindale, The Extra Pharmacopoeia, 30th ed). Cyclosporine binds to cyclophilin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Cyclosporine also inhibits lymphokine production and interleukin release. In ophthalmic applications, the precise mechanism of action is not known. Cyclosporine emulsion is thought to act as a partial immunomodulator in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.
Dược Động Học :
▧ Absorption :
The absorption of cyclosporine from the gastrointestinal tract is incomplete and variable. The extent of absorption is dependent on the individual patient, the patient population, and the formulation. The absolute bioavailability of cyclosproine administered as Sandimmune® is dependent on the patient population, estimated to be less than 10% in liver transplant patients and as great as 89% in some renal transplant patients. Compared to an intravenous infusion, the absolute bioavailability of the oral solution is approximately 30% based upon the results in 2 patients. The cyclosporine capsules and oral solution are bioequivalent. The time of peak blood concentrations (Tmax) following oral administration of cyclosporine [modified] ranged from 1.5 - 2.0 hours.
▧ Volume of Distribution :
The steady state volume of distribution during intravenous dosing has been reported as 3 to 5 L/kg in solid organ transplant recipients. Cyclosporine is excreted in human milk.
▧ Protein binding :
In the plasma, approximately 90% is bound to proteins, primarily lipoproteins. In blood, the distribution is concentration dependent. Approximately 33% to 47% is in plasma, 4% to 9% in lymphocytes, 5% to 12% in granulocytes, and 41% to 58% in erythrocytes.
▧ Metabolism :
Hepatic, extensively metabolized by the cytochrome P450 3A enzyme system in the liver. It is also metabolized in the gastrointestinal tract and kidney to a lesser degree. The metabolites are significantly less potent than the parent compound. The major metabolites (M1, M9, and M4N) result from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively.
▧ Route of Elimination :
Elimination is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in the urine. Only 0.1% of the dose is excreted in the urine as unchanged drug.
▧ Half Life :
Biphasic and variable, approximately 7 hours (range 7 to 19 hours) in children and approximately 19 hours (range 10 to 27 hours) in adults.
▧ Clearance :
Following intravenous administration, the blood clearance of cyclosporine (assay: HPLC) is approximately 5 to 7 mL/min/kg in adult recipients of renal or liver allografts. Blood cyclosporine clearance appears to be slightly slower in cardiac transplant patients. The following are clearance parameters (CL/F) for select patient populations: * 593 ± 204 mL/min [De novo renal transplant patients, 597±174 mg/day] * 492 ± 140 mL/min [Stable renal transplant patients, 344±122 mg/day] * 577 ± 309 mL/min [De novo liver transplant, 458±190 mg/day] * 613 ± 196 mL/min [De novo rheumatoid arthritis, 182±55.6 mg/day] * 723 ± 186 mL/min [De novo psoriasis, 189±69.8 mg/day] * 285 ± 94 mL/min [Stable Liver Transplant, Age 2 - 8, Dosed T.I.D 101±25 mg/day] * 378 ± 80 mL/min [Stable Liver Transplant, Age 8 - 15, Dosed B.I.D 188±55 mg/day] * 171 mL/min [Stable liver transplant, Age 3, Dosed B.I.D 120 mg/day] * 328 ± 121 mL/min [Stable liver transplant, Age 8 - 15, Dosed B.I.D 158±55 mg/day] * 418 ± 143 mL/min [Stable renal transplant, Age 7 - 15, Dosed B.I.D 328±83 mg/day]
Độc Tính : The oral LD50 is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD50 is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.
Chỉ Định : For treatment of transplant (kidney, liver, and heart) rejection, rheumatoid arthritis, severe psoriasis.
Tương Tác Thuốc :
  • Acetazolamide Acetazolamide may increase the effect and toxicity of cyclosporine.
  • Aliskiren Avoid combination because cyclosporine increases aliskiren serum concentration.
  • Allopurinol Allopurinol increases the effect and toxicity of cyclosporine
  • Amiodarone Amiodarone may increase the therapeutic and adverse effects of cyclosporine.
  • Amobarbital The barbiturate, amobarbital, increases the effect of cyclosporine.
  • Amphotericin B Monitor for nephrotoxicity
  • Amprenavir The protease inhibitor, amprenavir, may increase the effect of cyclosporine.
  • Aprobarbital The barbiturate, aprobarbital, increases the effect of cyclosporine.
  • Atazanavir Atazanavir may increase the therapeutic and adverse effects of cyclosporine.
  • Atorvastatin Possible myopathy and rhabdomyolysis
  • Azithromycin The macrolide, azithromycin, may increase the effect of cyclosporine.
  • Bezafibrate Cyclosporine may enhance the nephrotoxic effect of fibric acid derivatives like bezafibrate. Fibric acid derivatives may decrease the serum concentration of cyclosporine. Extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary.
  • Bosentan Cyclosporine may increase the effect and toxicity of bosentan.
  • Bupropion Bupropion may decrease the therapeutic effect of cyclosporine.
  • Butabarbital The barbiturate, butabarbital, increases the effect of cyclosporine.
  • Butalbital The barbiturate, butalbital, increases the effect of cyclosporine.
  • Butethal The barbiturate, butethal, increases the effect of cyclosporine.
  • Carbamazepine Carbamazepine may decrease the therapeutic effect of cyclosporine.
  • Carvedilol Carvedilol may increase the therapeutic and adverse effects of cyclosporine.
  • Caspofungin Cyclosporine increases the effect and toxicity of caspofungin
  • Cerivastatin Possible myopathy and rhabdomyolysis
  • Chloramphenicol Chloramphenicol may increase the effect of cyclosporine.
  • Chloroquine Chloroquine may increase the therapeutic and adverse effects of cyclosporine.
  • Cilastatin Imipenem increases the effect and toxicity of cyclosporine
  • Ciprofloxacin Ciprofloxacin may increase the effect and toxicity of cyclosporine.
  • Clarithromycin The macrolide, clarithromycin, may increase the effect of cyclosporine.
  • Clindamycin Clindamycin may decrease the therapeutic effect of cyclosporine.
  • Colchicine Increased toxicity of both drugs
  • Danazol The androgen, danazol, may increase the effect and toxicity of cyclosporine.
  • Diclofenac Monitor for nephrotoxicity
  • Digoxin Cyclosporine may increase the effect of digoxin.
  • Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, increases the effect of cyclosporine.
  • Diltiazem Diltiazem may increase the effect and toxicity of cyclosporine.
  • Dronedarone Cyclosporine is a strong CYP3A4 inhibitor in which concomitant use with dronedarone will significantly increase its exposure. Avoid concomitant use.
  • Efavirenz Efavirenz decreases the levels of cyclosporine
  • Erythromycin The macrolide, erythromycin, may increase the effect of cyclosporine.
  • Ethinyl Estradiol The contraceptive increases the effect and toxicity of cyclosporine
  • Ethotoin The hydantoin decreases the effect of cyclosporine
  • Etodolac Monitor for nephrotoxicity
  • Etoposide Cyclosporine may increase the therapeutic and adverse effects of etoposide.
  • Ezetimibe Cyclosporine may increase the therapeutic and adverse effects of ezetimibe.
  • Fenoprofen Monitor for nephrotoxicity
  • Fidaxomicin Cyclosporin is an inhibitor of p-glycoprotein and concomitant therapy will result in a increase in Cmax and AUC of fidaxomicin and its metabolite.
  • Fluconazole Fluconazole may increase the therapeutic and adverse effects of the cyclosporine.
  • Fluoxetine The antidepressant increases the effect and toxicity of cyclosporine
  • Flurbiprofen Monitor for nephrotoxicity
  • Fluvastatin Possible myopathy and rhabdomyolysis
  • Fosamprenavir The protease inhibitor, fosamprenavir, may increase the effect of cyclosporine.
  • Foscarnet Monitor for nephrotoxicity
  • Fosphenytoin The hydantoin decreases the effect of cyclosporine
  • Glimepiride The sulfonylurea, glimepiride, may increase the effect of cyclosporine.
  • Glipizide The sulfonylurea, glipizide, may increase the effect of cyclosporine.
  • Glyburide The sulfonylurea, glibenclamide, may increase the effect of cyclosporine.
  • Griseofulvin Griseofulvin decreases the effect of cyclosporine
  • Heptabarbital The barbiturate, heptabarbital, increases the effect of cyclosporine.
  • Hexobarbital The barbiturate, hexobarbital, increases the effect of cyclosporine.
  • Ibuprofen Monitor for nephrotoxicity
  • Imatinib Imatinib increases the effect and toxicity of cyclosporine
  • Imipenem Imipenem increases the effect and toxicity of cyclosporine
  • Indinavir The protease inhibitor, indinavir, may increase the effect of cyclosporine.
  • Indomethacin Monitor for nephrotoxicity
  • Itraconazole Itraconazole may increase the effect of cyclosporine.
  • Josamycin The macrolide, josamycin, may increase the effect of cyclosporine.
  • Ketoconazole Ketoconazole may increase the effect of cyclosporine.
  • Ketoprofen The NSAID, ketoprofen, may increase the serum concentration of cyclosporine. Ketoprofen may also increase the nephrotoxicity of cyclosporine.
  • Lovastatin Possible myopathy and rhabdomyolysis
  • Meclofenamic acid Monitor for nephrotoxicity
  • Mefenamic acid Monitor for nephrotoxicity
  • Melphalan Melphalan increases toxicity of cyclosporine
  • Mephenytoin The hydantoin decreases the effect of cyclosporine
  • Mestranol The contraceptive increases the effect and toxicity of cyclosporine
  • Methohexital The barbiturate, methohexital, increases the effect of cyclosporine.
  • Methotrexate Cyclosporine may increase the effect and toxicity of methotrexate.
  • Methylphenidate Methylphenidate increases the effect and toxicity of cyclosporine
  • Methylphenobarbital The barbiturate, methylphenobarbital, increases the effect of cyclosporine.
  • Metoclopramide Metoclopramide increases serum levels of cyclosporine
  • Modafinil Modafinil decreases the effect of cyclosporine
  • Muromonab Muromonab increases the levels of cyclosporine
  • Nabumetone Monitor for nephrotoxicity
  • Nafcillin Nafcillin alters serum levels of cyclosporine
  • Naproxen Monitor for nephrotoxicity
  • Nefazodone The antidepressant increases the effect and toxicity of cyclosporine
  • Nelfinavir The protease inhibitor, nelfinavir, may increase the effect of cyclosporine.
  • Nicardipine Nicardipine increases the effect and toxicity of cyclosporine
  • Nifedipine Increased risk of gingivitis
  • Norfloxacin Norfloxacin may increase the effect and toxicity of cyclosporine.
  • Octreotide Octreotide decreases the effect of cyclosporine
  • Omeprazole Omeprazole increases the effect and toxicity of cyclosporine
  • Orlistat Orlistat decreases the effect of cyclosporine
  • Oxaprozin Monitor for nephrotoxicity
  • Oxcarbazepine Oxcarbazepine decreases the effect of cyclosporine
  • Pentobarbital The barbiturate, pentobarbital, increases the effect of cyclosporine.
  • Phenobarbital The barbiturate, phenobarbital, may decrease the therapeutic effect of cyclosporine by increasing its metabolism.
  • Phenytoin The hydantoin decreases the effect of cyclosporine
  • Piroxicam Monitor for nephrotoxicity
  • Pitavastatin Cyclosporine decreases metabolism of pitavastatin thus increasing serum concentration. Avoid concomitant drug therapy.
  • Posaconazole Increased level of cyclosporine
  • Pravastatin Possible myopathy and rhabdomyolysis
  • Primidone The barbiturate, primidone, increases the effect of cyclosporine.
  • Probucol Probucol decreases the effect of cyclosporine
  • Propafenone Propafenone increases the effect and toxicity of cyclosporine
  • Pyrazinamide Pyrazinamide decreases the effect of cyclosporine
  • Quinidine barbiturate The barbiturate, quinidine barbiturate, increases the effect of cyclosporine.
  • Quinupristin Synercid increases the effect of cyclosporine
  • Repaglinide Cyclosporine may increase the therapeutic and adverse effects of repaglinide.
  • Rifabutin The rifamycin decreases the effect of cyclosporine
  • Rifampicin The rifamycin decreases the effect of cyclosporine
  • Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
  • Ritonavir The protease inhibitor, ritonavir, may increase the effect of cyclosporine.
  • Rosuvastatin Cyclosporine may increase the serum concentration of rosuvastatin. Limit rosuvastatin dosing to 5 mg/day and monitor for changes in the therapeutic and adverse effects of rosuvastatin if cyclosporine is initiated, discontinued or dose changed.
  • Roxithromycin The macrolide, roxithromycin, may increase the effect of cyclosporine.
  • Saquinavir The protease inhibitor, saquinavir, may increase the effect of cyclosporine.
  • Secobarbital The barbiturate, secobarbital, increases the effect of cyclosporine.
  • Sevelamer Sevelamer decreases the effect of cyclosporine
  • Sibutramine Sibutramine increases the effect and toxicity of cyclosporine
  • Simvastatin Possible myopathy and rhabdomyolysis
  • Sirolimus Increases the effect and toxicity of sirolimus
  • St. John's Wort St. John's Wort decreases the effect of cyclosporine
  • Sulfadiazine The sulfonamide decreases the effect of cyclosporine
  • Sulfamethazine The sulfonamide decreases the effect of cyclosporine
  • Sulfamethoxazole The sulfonamide decreases the effect of cyclosporine
  • Sulfasalazine The sulfonamide decreases the effect of cyclosporine
  • Sulfinpyrazone Sulfinpyrazone decreases the effect of cyclosporine
  • Sulindac The NSAID, sulindac, may increase the nephrotoxic effect of cyclosporine. Sulindac may increase the serum concentration of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine levels and nephrotoxicity during concomitant therapy.
  • Tacrolimus Additive renal impairment may occur during concomitant therapy with cyclosporine. Combination therapy should be avoided.
  • Talbutal The sulfonamide decreases the effect of cyclosporine
  • Tamsulosin Cyclosporine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Cyclosporine is initiated, discontinued, or dose changed.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Must monitor levels closely with concomitant therapy.
  • Telithromycin Telithromycin may reduce clearance of cyclosporine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of cyclosporine if telithromycin is initiated, discontinued or dose changed.
  • Tenoxicam Monitor for nephrotoxicity
  • Terbinafine Terbinafine may decrease the plasma concentration and therapeutic effect of cyclosporine.
  • Testolactone The androgen, Testolactone, may increase the hepatotoxicity of Cyclosporine. Testolatone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
  • Testosterone The androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
  • Testosterone Propionate The androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
  • Thiopental Thiopental may increase the metabolism and clearance of Cyclosporine. Monitor for changes in the therapeutic/adverse effects of Cyclosporine if Thiopental is initiated, discontinued or dose changed.
  • Tiaprofenic acid Tiaprofenic acid may increase the nephrotoxicity and/or the serum concentration of cyclosporine. Consider altnerate therapy or monitor for increased cyclosporine concentrations and nephrotoxicity during concomitant therapy.
  • Ticlopidine Ticlopidine decreases the effect of cyclosporine
  • Tipranavir Tipranavir may affect the efficacy/toxicity of Cyclosporine.
  • Tobramycin Increased risk of nephrotoxicity
  • Tofacitinib Cyclosporin (and other strong immunosuppressants), when used in combination with tofacitinib, may increase the risk of added immunosuppression and infection. It is recommended to avoid concurrent therapy.
  • Tolmetin Tolmetin may increase the serum concentration of cyclosporine and/or increase the nephrotoxicity of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine serum concentration and nephrotoxicity during concomitant therapy.
  • Tolterodine Cyclosporine may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Topotecan The p-glycoprotein inhibitor, Cyclosporine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Tramadol Cyclosporine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trandolapril The ACE inhibitor, Trandolapril, may increase the nephrotoxicity of Cyclosporine.
  • transdermal testosterone gel The androgen, Testosterone, may increase the hepatotoxicity of Cyclosporine. Testosterone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Trazodone The CYP3A4 inhibitor, Cyclosporine, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Cyclosporine is initiated, discontinued or dose changed.
  • Troglitazone Troglitazone decreases the effect of the immunosuppressant
  • Troleandomycin The macrolide, troleandomycin, may increase the effect of cyclosporine.
  • Ursodeoxycholic acid Ursodiol increases the levels of cyclosporine
  • Verapamil Verapamil may increase the serum concentration of cyclosporine by inhibiting CYP3A4-mediated metabolism of cyclosporine. Monitor for changes in the therapeutic/adverse effects of cyclosporine if verapamil is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of cyclosporine by decreasing its metabolism. Consider reducing the dose of cyclosporine. Monitor cyclosporine serum concentrations and therapeutic and toxic effects if initiating, discontinuing or adjusting voriconazole therapy.
Liều Lượng & Cách Dùng : Capsule - Oral - 25 mg, 50 mg, 100 mg
Emulsion - Ophthalmic - 0.05%
Injection, solution - Intravenous - 50 mg/mL
Solution - Oral - 100 mg/mL
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Abbott Labs
    Sản phẩm biệt dược : Gengraf
  • Công ty : Novartis
    Sản phẩm biệt dược : Neoral
  • Công ty : Allergan Inc.
    Sản phẩm biệt dược : Restasis
  • Công ty : Novartis
    Sản phẩm biệt dược : Sandimmune
  • Công ty :
    Sản phẩm biệt dược : Sangcya
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00091
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C05086
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00184
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0240-15
PharmGKB
http://www.pharmgkb.org/drug/PA449167
Wikipedia
http://en.wikipedia.org/wiki/Cyclosporine
RxList
http://www.rxlist.com/cgi/generic/cyclosporine.htm
Drugs.com
http://www.drugs.com/cdi/cyclosporine-drops.html
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