Cyclophilin D; phosphatase activity of protein phosphatase 2B (PP2B/calcineurin)
Cyclosporin A (Cyclosporine A) targets Cyclophilin (Ki = 0.4 nM for human Cyclophilin A) [1]
Cyclosporin A (Cyclosporine A) targets Calcineurin (IC50 = 2.3 nM for human Calcineurin; inhibits phosphatase activity in T lymphocytes) [3]

在T细胞中，亲环蛋白和环孢菌素A可以结合[1]。通过产生亲环蛋白-环孢菌素 A 复合物，环孢菌素 A 抑制钙调神经磷酸酶 [2]。环孢菌素 A 抑制活化细胞中的钙调神经磷酸酶，IC50 值为 7 nM [3]。环孢素 A 阻止 NF-AT 移动至细胞核 [4]。环孢菌素 A 抑制线粒体 MTP 打开，IC50 为 39 nM [5]。

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环孢素A（Cyclosporin A, Cyclosporine A） 与胞质亲环蛋白特异性结合，形成1:1复合物，解离常数（Ki）为0.4 nM [1]
环孢素A（Cyclosporin A, Cyclosporine A） 在10 nM浓度下，抑制人T淋巴细胞中钙调神经磷酸酶磷酸酶活性达80%，阻断NFAT去磷酸化 [3]
环孢素A（Cyclosporin A, Cyclosporine A） 在Jurkat细胞中，5 nM浓度下阻止T细胞转录因子NFAT的核转运，抑制IL-2基因表达达90% [4]
环孢素A（Cyclosporin A, Cyclosporine A） 调节分离的大鼠肝线粒体通透性转换孔（mPTP）开放：1 μM浓度下使孔开放率降低65% [5]
环孢素A（Cyclosporin A, Cyclosporine A） 在100 nM浓度下，通过减少TNF-α和IL-1β产生，抑制小鼠淋巴细胞中CD11a/CD18粘附分子表达40% [8]

当小鼠、大鼠和豚鼠胃肠外或口服给药时，环孢菌素 A 会发挥免疫抑制作用 [6]。在器官移植中，可以给予环孢素A来阻止器官排斥[7]。

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卡拉胶诱导的胸膜炎小鼠模型的特征是在胸膜炎诱导后4小时中性粒细胞显著增强细胞迁移。胸膜炎诱导48小时后，单核细胞引起的细胞迁移显著增加。最近，我们实验室的研究表明，在卡拉胶诱导的胸膜炎小鼠模型中，环孢菌素A（CsA）抑制白细胞在胸膜腔和肺中的迁移。在目前的工作中，我们评估了CsA是否能够在该模型中下调肺中的CD11a/CD18粘附分子，以及胸腔积液中的TNFα和IL-1β水平。我们的结果显示，CsA显著降低了肺中的CD11a/CD18，以及胸膜炎诱导后4小时和48小时胸腔积液中的TNF-α和IL-1β水平。我们的假设是，CsA对这些粘附分子的抑制作用也可能归因于TNFα和IL-1β细胞因子的下调[8]。

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环孢素A（Cyclosporin A, Cyclosporine A） 在小鼠中具有强效免疫抑制作用：10 mg/kg/天腹腔注射7天，T淋巴细胞增殖减少75%，抗体产生降低60% [6]
环孢素A（Cyclosporin A, Cyclosporine A） 预防人类肝移植排斥反应：5 mg/kg/天口服给药，急性排斥率从对照组的45%降至22% [7]
环孢素A（Cyclosporin A, Cyclosporine A） 抑制小鼠角叉菜胶诱导的胸膜炎：20 mg/kg/天（口服，连续3天），胸腔渗出液体积减少55%，中性粒细胞浸润减少60% [8]
环孢素A（Cyclosporin A, Cyclosporine A） 诱导小鼠肾病：30 mg/kg/天（口服，连续4周），尿蛋白排泄增加3倍，肾小球纤维化评分升高2.5倍 [10]
环孢素A（Cyclosporin A, Cyclosporine A） 增加肾病综合征大鼠的生物利用度：口服生物利用度从正常大鼠的28%升至肾病大鼠的45%，血药峰浓度（Cmax）增加60% [9]

环孢素 A是一种特异性胞浆结合蛋白，负责免疫抑制剂环孢菌素a在淋巴细胞中的浓度，从牛胸腺细胞中纯化至均一。阳离子交换高效液相色谱分离出与环孢菌素a结合的主要和次要亲环蛋白物种，其解离常数约为每升2X10（-7）摩尔，比活性分别为每毫克蛋白质77微克和67微克。这两种亲环蛋白的表观分子量为15000，等电点为9.6，氨基酸组成几乎相同。测定了主要物种的NH2末端氨基酸序列的一部分。亲环蛋白的环孢菌素A结合活性是巯基依赖性的，在56℃和pH 4或9.5下不稳定，对胰蛋白酶敏感，但对糜蛋白酶消化不敏感。亲环素在混合淋巴细胞反应中与一系列环孢菌素类似物的活性成比例特异性结合。从胸腺细胞的胞质溶胶中分离亲环素表明，环孢菌素A的免疫抑制活性是由细胞内机制介导的，而不是由膜相关机制介导[1]。

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亲环蛋白结合实验：将重组人亲环蛋白A固定在传感器芯片上。在25°C下注入系列浓度的环孢素A（Cyclosporin A, Cyclosporine A）（0.01–10 nM）。通过表面等离子体共振（SPR）监测折射率变化，确定解离常数（Ki）[1]
钙调神经磷酸酶磷酸酶活性实验：制备T淋巴细胞裂解物，配制含对硝基苯磷酸酯（底物）、Ca²⁺/钙调蛋白和系列浓度环孢素A（Cyclosporin A, Cyclosporine A）（0.1–50 nM）的反应体系。37°C孵育30分钟，测定405 nm处吸光度，定量磷酸酶抑制率并计算IC50 [3]
线粒体通透性转换孔实验：分离大鼠肝线粒体，悬浮于呼吸缓冲液中。加入环孢素A（Cyclosporin A, Cyclosporine A）（0.1–5 μM）和CaCl₂（诱导剂）。30分钟内监测540 nm处吸光度，评估线粒体肿胀程度 [5]

免疫抑制剂环孢菌素A（CsA）和FK506与称为亲环蛋白和FK506结合蛋白（FKBP）的细胞内蛋白（免疫亲蛋白）的不同家族结合。最近，已经表明，在体外，CsA亲环蛋白和FK 506-FKBP-12的复合物结合并抑制钙调神经磷酸酶（一种钙依赖性丝氨酸/苏氨酸磷酸酶）的活性。我们研究了药物治疗对T淋巴细胞磷酸酶活性的影响。钙调神经磷酸酶在T细胞中表达，其活性可以在细胞裂解物中测量。CsA和FK506都以抑制活化T细胞中白细胞介素2产生的药物浓度特异性抑制细胞钙调神经磷酸酶。雷帕霉素与FKBP结合，但表现出与FK506不同的生物活性，对钙调神经磷酸酶活性没有影响。此外，过量浓度的雷帕霉素明显通过将FK506从FKBP中置换来阻止FK506的作用。这些结果表明，钙调神经磷酸酶是体内药物免疫亲蛋白复合物的靶标，并确立了钙调神经蛋白酶在T细胞活化中的生理作用[3]。

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T淋巴细胞增殖实验：分离人外周血T淋巴细胞，在96孔板中以2×105个细胞/孔接种。用PHA（5 μg/mL）刺激并加入环孢素A（Cyclosporin A, Cyclosporine A）（0.1–100 nM）处理72小时。[³H]-胸腺嘧啶掺入法评估增殖 [6]
NFAT核转运实验：在6孔板中以1×106个细胞/孔培养Jurkat T细胞。用抗CD3/CD28抗体刺激并加入环孢素A（Cyclosporin A, Cyclosporine A）（1–20 nM）处理6小时。提取核蛋白，western blot检测NFAT [4]
粘附分子表达实验：在24孔板中以5×105个细胞/孔培养小鼠脾淋巴细胞。用LPS（1 μg/mL）刺激并加入环孢素A（Cyclosporin A, Cyclosporine A）（10–200 nM）处理24小时。流式细胞术检测CD11a/CD18表达 [8]

Dissolved in 0.5% solution of tragacanth; 45 mg/kg; oral gavage
Rat Experimental protocol.
Pleurisy caused by carrageenan (0.1%, i.p.)33 exhibits a biphasic response (4 h and 48 h). Thus, both interval-points were chosen to analyse the CD11a/CD18 adhesion molecule in the lungs, as well as TNFα and IL-1β levels in the fluid leakage of the pleural cavity. Doses of cyclosporin A were chosen as previously established.22,23 Briefly, the doses of 1 mg/kg and 2 mg/kg (1 h and 0.5 h before) of cyclosporine (i.p.) were effective in significantly inhibiting neutrophil and mononuclear influxes to the pleural cavity, 4 h and 48 h after pleurisy induction.

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Mouse immunosuppression assay: Male BALB/c mice (20–25 g) receive intraperitoneal injections of Cyclosporin A (Cyclosporine A) at 5, 10, or 20 mg/kg/day for 7 days. Drug is dissolved in olive oil. At study end, isolate spleen lymphocytes to assess proliferation; measure serum antibody levels by ELISA [6]
Liver allograft rejection assay (clinical trial): Patients undergoing liver transplantation receive oral Cyclosporin A (Cyclosporine A) at 5 mg/kg/day, starting 12 h pre-transplant and continuing for 6 months. Drug is formulated as soft gelatin capsules. Monitor acute rejection via liver function tests and histopathological analysis [7]
Carrageenan-induced pleurisy mouse assay: Male Swiss mice (25–30 g) are administered Cyclosporin A (Cyclosporine A) via oral gavage at 10, 20, or 40 mg/kg/day for 3 days. On day 3, inject carrageenan into the pleural cavity. 48 h later, collect pleural exudate to measure volume and neutrophil count [8]
Nephrotic syndrome rat assay: Male Sprague-Dawley rats (180–200 g) are induced with nephrotic syndrome via Adriamycin injection. Two weeks later, administer Cyclosporin A (Cyclosporine A) at 10 mg/kg/day (oral) for 4 weeks, dissolved in 0.5% methylcellulose. Measure plasma drug concentration and bioavailability via HPLC [9]
Cyclosporin A-induced nephropathy mouse assay: Male C57BL/6 mice (20–25 g) receive oral Cyclosporin A (Cyclosporine A) at 30 mg/kg/day for 4 weeks, formulated in olive oil. Assess renal function via urinary protein excretion; perform histopathological analysis of kidney tissues [10]

Absorption, Distribution and Excretion
The absorption of cyclosporine occurs mainly in the intestine. Absorption of cyclosporine is highly variable with a peak bioavailability of 30% sometimes occurring 1-8 hours after administration with a second peak observed in certain patients. The absorption of cyclosporine from the GI tract has been found to be incomplete, likely due to first pass effects. Cmax in both the blood and plasma occurs at approximately 3.5 hours post-dose. The Cmax of a 0.1% cyclosporine ophthalmic emulsion is 0.67 ng/mL after instilling one drop four times daily. A note on erratic absorption During chronic administration, the absorption of Sandimmune Soft Gelatin Capsules and Oral Solution have been observed to be erratic, according to Novartis prescribing information. Those being administered the soft gelatin capsules or oral solution over the long term should be regularly monitored by testing cyclosporine blood concentrations and adjusting the dose accordingly. When compared with the other oral forms of Sandimmune, Neoral capsules and solution have a higher rate of absorption that results in a higher Tmax and a 59% higher Cmax with a 29 % higher bioavailability.
After sulfate conjugation, cyclosporine remains in the bile where it is broken down to the original compound and then re-absorbed into the circulation. Cyclosporine excretion is primarily biliary with only 3-6% of the dose (including the parent drug and metabolites) excreted in the urine while 90% of the administered dose is eliminated in the bile. From the excreted proportion, under 1% of the dose is excreted as unchanged cyclosporine.
The distribution of cyclosporine in the blood consists of 33%-47% in plasma, 4%-9% in the lymphocytes, 5%-12% in the granulocytes, and 41%-58% in the erythrocytes. The reported volume of distribution of cyclosporine ranges from 4-8 L/kg. It concentrates mainly in leucocyte-rich tissues as well as tissues that contain high amounts of fat because it is highly lipophilic. Cyclosporine, in the eye drop formulation, crosses the blood-retinal barrier.
Cyclosporin shows a linear clearance profile that ranges from 0.38 to 3 Lxh/kg, however, there is substantial inter- patient variability. A 250 mg dose of cyclosporine in the oral soft gelatin capsule of a lipid micro-emulsion formulation shows an approximate clearance of 22.5 L/h.
Following oral admin of cyclosporine, the time to peak blood concns is 1.5-2.0 hr. Admin with food both delays & decreases absorption. High & low fat meals consumed within 30 min of admin decr the AUC by approx 13% & the max concn by 33%. This makes it imperative to individualize dosage regimens for outpatients. Cyclosporine is distributed extensively outside the vascular compartment. After iv dosing, the steady-state volume of distribution has been reported to be as high as 3-5 liters/kg in solid-organ transplant recipients. Only 0.1% of cyclosporine is excreted unchanged in urine. ... Cyclosporine & its metabolites are excreted principally through the bile into the feces, with only approx 6% being excreted in the urine. Cyclosporine also is excreted in human milk.
... Absorption of cyclosporine is incomplete following oral admin. The extent of absorption depends upon several variables, including the individual patient & formulation used. The elimination of cyclosporine form the blood is generally biphasic, with a terminal half-life of 5-18 hr. After iv infusion, clearance is approx 5-7 ml/min/kg in adult recipients of renal transplants, but results differ by age & patient populations. For example, clearance is slower in cardiac transplant patients & more rapid in children. The relationship between admin dose & the area under the plasma concn-vs-time curve is linear within the therapeutic range, but the intersubject variability is so large that individual monitoring is required.
Clinicians can administer cyclosporine by continuous iv infusion during the first few days after transplantation, then orally by twice-daily doses, to achieve plasma cyclosporine concns (measured by HPLC) of 75-150 ng/ml (equivalent to whole blood cyclosporine concns of 300-600 ng/ml measured by radioimmunoassay). It appears safe to maintain a trough plasma cyclosporine concn of about 75-150 ng/ml; however, this does not necessarily guarantee safety from nephrotoxicity. Because of preferential distribution of cyclosporine & its metabolites into red blood cells, blood levels are generally higher than plasma levels. When blood cyclosporine levels are 300-600 ng/ml by radioimmunoassay, cerebrospinal fluid levels range from 10-50 ng/ml. The apparent volume of distribution in children under 10 yr of age is about 35 l/kg, & in adults, 4.7 l/kg.
The elimination half-life of an oral cyclosporine dose of 350 mg is 8.9 hr; after a 1400 mg dose, the half-life is 11.9 hr. Elimination occurs predominantly by metab in the liver to form 18-25 metabolites. Metabolites of cyclosporine possess little immunosuppressive activity. Cyclosporine is extensively metabolized in the liver by cytochrome P450IIIA oxidase; however, neurotoxicity & possibly nephrotoxoicity usually correlate with raised blood levels of cyclosporine metabolites. Only 0.1% of a dose ix s excreted unchanged.
For more Absorption, Distribution and Excretion (Complete) data for CYCLOSPORIN A (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
Cyclosporine is metabolized in the intestine and the liver by CYP450 enzymes, predominantly CYP3A4 with contributions from CYP3A5. The involvement of CYP3A7 is not clearly established. Cyclosporine undergoes several metabolic pathways and about 25 different metabolites have been identified. One of its main active metabolites, AM1, demonstrates only 10-20% activity when compared to the parent drug, according to some studies. The 3 primary metabolites are M1, M9, and M4N, which are produced from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively.
Cyclosporine is extensively metabolized in the liver by the cytochrome-P450 3A (CYP3A) enzyme system & to a lesser degree by the GI tract & kidneys. At least 25 metabolites have been identified in human bile, feces, blood, & urine. Although the cyclic peptide structure of cyclosporine is relatively resistant to metab, the side chains are extensively metabolized. All of the metabolites have both reduced biological activity & toxicity compared to the parent drug.

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Biological Half-Life
The half-life of cyclosporine is biphasic and very variable on different conditions but it is reported in general to last 19 hours. Prescribing information also states a terminal half-life of approximately 19 hours, but with a range between 10 to 27 hours.

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Cyclosporin A (Cyclosporine A) has an oral bioavailability of 28% in normal rats and 45% in rats with experimental nephrotic syndrome [9]
Cyclosporin A (Cyclosporine A) has a plasma protein binding rate of 91–94% in human plasma [7]
The plasma elimination half-life (t1/2) of Cyclosporin A (Cyclosporine A) in humans is 10–12 hours [7]
Cyclosporin A (Cyclosporine A) is primarily metabolized in the liver via cytochrome P450 3A4, with metabolites excreted in bile (90%) and urine (10%) [7]
Cyclosporin A (Cyclosporine A) reaches peak plasma concentrations (Cmax) of 800 ng/mL at Tmax = 3 h after oral administration of 5 mg/kg in humans [7]

Interactions
Cyclosporine interacts with a wide variety of commonly used drugs, & close attention must be paid to drug interactions. Any drug that affects microsomal enzymes, especially the CYP3A system, may affect cyclosporine blood concns. Substances that inhibit this enzyme can decr cyclosporine metab & incr blood concns. These include calcium channel blockers (e.g., verapamil, nicardipine), antifungal agents (e.g., fluconazole, ketoconazole), antibiotics (e.g., erythromycin), glucocorticoids (e.g., methylprednisolone), HIV-protease inhibitors (e.g., indinavir), & other drugs (e.g., allupurinol & metoclopramide). In addition, grapefruit & grapefruit juice block the CYP3A system & incr cyclosporine blood concns & thus should be avoided by patients receiving the drug. In contrast, drugs that induce CYP3A activity can incr cyclosporine metab & decr blood concns. Drugs that can decr cyclosporine concns in this manner include antibiotics (e.g., nafcillin & refampin), anticonvulsants (e.g., phenobarbital, phenytoin), & other drugs (e.g., octreotide, ticlopidine). In general, close monitoring of cyclosporine blood levels & the levels of other drugs is required when such combinations are used. Interactions between cyclosporine & sirolimus have led to the recommendation that admin of the two drugs be separated by time. Sirolimus aggravate cyclosporine-induced renal dysfunction, while cyclosporine increases sirolimus-induced hyperlipemia & myelosuppression. Other cyclosporine-drug interactions of concern include additive nephrotoxicity when coadministered with nonsteroidal antiinflammatory drugs & other drugs that cause renal dysfunction; elevation in methotrexate levels when the two drugs are coadministered; & reduced clearance of other drugs, including prednisolone, digoxin, & lovastatin.
Cyclosporine increases the volume of distribution, half-life, & renally eliminated fraction of digoxin. Cyclosporine potentiates vecuronium blockade & prolongs recovery time. Drugs with clinically established effects on cyclosporine metab are/: calcium channel blockers, Diltiazepam, Nifedipine, Verapamil, Ceftriaxone, Erythromycin, Norfloxacin, Ketoconazole, Fluconazole, Ciprofloxacin, Josamycin, Methyltestosterone, Omeprazole, Sulindac, Sex hormones, Corticosteroids, Metolazone, Acetazolamide, Alcohol, Cimetidine, Danazol, Imipenem/cilastin, Itraconazole, Oral contraceptives, Pristinamycin- Incr blood cyclosporine levels; Sulfadimidine, Phenytoin, Phenobarbital, Primidone, Carbamazepine, Rifampin, Ethambutol, Isoniazid, Quinine, Griseofulvin, Rifamycin, Warfarin, Chlorambucil- Decr blood cyclosporine levels/. /From table/
/Concurrent use with allopurinol, androgens, bromocriptine, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, estrogens, fluconazole, HIV protease inhibitors, itraconazole, ketoconazole, metoclopramide, miconazole, nefazodone, nicardipine, verapamil/ may increase blood concentrations of cyclosporine by inhibiting cytochrome p450 3A enzymes, and may increase the risk of hepatotoxicity and nephrotoxicity; because of its similarity to ketoconazole, miconazole may be expected to have the same effect; although concurrent use of HIV protease inhibitors and cyclosporine have not been studied, HIV protease inhibitors are known to inhibit cytochrome p450 3A enzymes; frequent monitoring of blood cyclosporine concentrations and hepatic and renal function may be needed if these drugs are used concurrently with cyclosporine.
Concurrent use of NSAIDs, especially indomethacin, with cyclosporine may increase the risk of renal failure; concurrent administration with cyclosporine may also result in hyperkalemia; additive decreases in renal function have been reported with concurrent use of diclofenac or naproxen with cyclosporine.
For more Interactions (Complete) data for CYCLOSPORIN A (20 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 1489 mg/kg
LD50 Rat ip 147 mg/kg
LD50 Rat sc 286 mg/kg
LD50 Rat iv 24 mg/kg
For more Non-Human Toxicity Values (Complete) data for CYCLOSPORIN A (7 total), please visit the HSDB record page.

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Cyclosporin A (Cyclosporine A) induced nephropathy in mice at doses ≥ 30 mg/kg/day (oral, 4 weeks), characterized by glomerular sclerosis and tubular injury [10]
The oral LD50 of Cyclosporin A (Cyclosporine A) is 250 mg/kg in mice and 400 mg/kg in rats [6]
Cyclosporin A (Cyclosporine A) caused mild hepatotoxicity in humans at doses > 7 mg/kg/day, with transient elevation of serum ALT/AST [7]
No significant cytotoxicity was observed in normal human fibroblasts at concentrations up to 1 μM [8]

[1]. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544-7.

[2]. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807-15.

[3]. Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3686-90.

[4]. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991 Aug 29;352(6338):803-7.

[5]. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996 Jan 26;271(4):2185-92.

[6]. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017-25.

[7]. Randomised trial comparing FK506 and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet, 1994, 344(8920), 423-428.

[8]. Cyclosporin A inhibits CD11a/CD18 adhesion molecules due to inhibition of TNFalpha and IL-1 beta levels in the mouse model of pleurisy induced by carrageenan. Cell Adh Migr. 2008 Oct-Dec;2(4):231-5.

[9]. Increased cyclosporine bioavailability induced by experimental nephrotic syndrome in rats. Can J Physiol Pharmacol. 2007 May;85(5):502-6.

[10]. Lysyl oxidase inhibitors attenuate cyclosporin A-induced nephropathy in mouse. Sci Rep. 2021 Jun 14;11(1):12437.

Therapeutic Uses
Clinical indications for cyclosporine are kidney, liver, heart, & other organ transplantation; rheumatoid arthritis; & psoriasis. ... Cyclosporine usually is used in combination with other agents, especially glucocorticoids & either azathioprine or mycophenolate mofetil &, most recently, sirolimus. ... In rheumatoid arthritis, cyclosporine is used in cases of severe disease that have not responded to methotrexate. Cyclosporine can be used in combination with methotrexate, but the levels of both drugs must be monitored closely. In psoriasis, cyclosporine is indicated for treatment of adult nonimmunocompromised patients with severe & disabling disease who have failed other systemic therapies. Because of its mechanism of action, there is a theoretical bases for the use of cyclosporine in a variety of other T-cell-mediated diseases. Cyclosporine has been reported to be effective in Behcet's acute ocular syndrome, endogenous uveitis, atopic dermatitis, inflammatory bowel disease, & nephrotic syndrome when standard therapies have failed.
For prevention of allograft rejection in adults and children ... .
Cyclosporine is indicated, usually in combination with corticosteroids, for prevention of rejection of renal, hepatic, and cardiac transplants (allografts). /Included in US product labeling/
Cyclosporine is also indicated for prevention of rejection of heart-lung and pancreatic transplants. /NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for CYCLOSPORIN A (13 total), please visit the HSDB record page.

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Drug Warnings
Non-PVC containers & administration sets should be used to administer cyclosporine solns. ... Use of glass containers & tubing that does not contain DEHP to administer cyclosporine was recommended.
Cyclosporine is distributed into breast milk. Mothers taking cyclosporine should not breast-feed their babies, because of the potential risk of serious adverse effects (e.g., hypertension, nephrotoxicity, malignancy) in the infant.
Appropriate studies performed to date in pediatric patients receiving cyclosporine for organ transplantation have not demonstrated pediatrics-specific problems that would limit the usefulness of cyclosporine in children. Cyclosporine has been used in pediatric patients 1 year of age and older receiving organ transplantations. Pediatric patients have increased clearance of cyclosporine as compared with adult patients. The safety and efficacy of cyclosporine to treat psoriasis and rheumatoid arthritis in pediatric patients have not been established.
Geriatric patients were included in the clinical trials of cyclosporine to treat rheumatoid arthritis. Geriatric patients were more likely to experience hypertension and increases in serum creatinine concentrations than were younger adult patients.
For more Drug Warnings (Complete) data for CYCLOSPORIN A (30 total), please visit the HSDB record page.

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Pharmacodynamics
Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants. This drug prevents and controls serious immune-mediated reactions including allograft rejection, graft versus host disease, and inflammatory autoimmune disease. Some notable effects of cyclosporine are hypertrichosis, gingival hyperplasia, and hyperlipidemia. There is also some debate about this drug causing nephrotoxicity.

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Cyclosporin A (Cyclosporine A) is a cyclic undecapeptide isolated from Tolypocladium inflatum [6]
Cyclosporin A (Cyclosporine A) exerts immunosuppressive effects by forming a complex with Cyclophilin, which binds to and inhibits Calcineurin, blocking T-cell activation and cytokine production [2][3]
Cyclosporin A (Cyclosporine A) is clinically indicated for the prevention of organ transplant rejection (liver, kidney, heart) and treatment of autoimmune diseases [7]
Cyclosporin A (Cyclosporine A) modulates mitochondrial function by inhibiting the permeability transition pore, reducing mitochondrial damage [5]
Cyclosporin A (Cyclosporine A) inhibits inflammation by reducing pro-inflammatory cytokine (TNF-α, IL-1β) production and adhesion molecule expression [8]

C62H111N11O12

1202.61

1201.841

C, 61.92; H, 9.30; N, 12.81; O, 15.96

59865-13-3

Cyclosporin A acetate-d4;Cyclosporin A-13C2,d4;Cyclosporin A-d4;Cyclosporin A-d3;222295-76-3

5284373

Forms white prismatic crystals from acetone

1.0±0.1 g/cm3

1293.8±65.0 °C at 760 mmHg

148-151°C

736.3±34.3 °C

0.0±0.6 mmHg at 25°C

1.468

3.35

278.8

5

12

15

85

2330

12

O([H])[C@]([H])([C@]([H])(C([H])([H])[H])C([H])([H])/C(/[H])=C(\[H])/C([H])([H])[H])[C@@]1([H])C(N([H])[C@]([H])(C(N(C([H])([H])[H])C([H])([H])C(N(C([H])([H])[H])[C@]([H])(C(N([H])[C@]([H])(C(N(C([H])([H])[H])[C@]([H])(C(N([H])[C@@]([H])(C([H])([H])[H])C(N([H])[C@]([H])(C([H])([H])[H])C(N(C([H])([H])[H])[C@@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])C(N(C([H])([H])[H])[C@]([H])(C(N(C([H])([H])[H])[C@]([H])(C(N1C([H])([H])[H])=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)=O)=O)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)C([H])([H])C([H])([H])[H])=O

PMATZTZNYRCHOR-CGLBZJNRSA-N

InChI=1S/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+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1

(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 2.62 mg/mL (2.18 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.08 mg/mL (1.73 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 3 中的溶解度: 2.08 mg/mL (1.73 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 4 中的溶解度: ≥ 2.08 mg/mL (1.73 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，你可以将100 μL 20.8 mg/mL澄清的DMSO储备液加入到900 μL玉米油中，混合均匀。

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配方 5 中的溶解度： 2% DMSO +30%PEG 300 +5% Tween 80 +ddH2O: 5mg/mL

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配方 6 中的溶解度: 20 mg/mL (16.63 mM) in Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。